愤怒情志特质与神经递质代谢酶基因多态性的关系研究
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摘要
目的：探讨愤怒情志特质与神经递质代谢酶基因多态性的关系,并分析愤怒情志特质各维度间的相关性。
方法：
1.状态-特质怒表达量表Ⅱ问卷调查
以河南中医学院在校正常大学生为调查对象,经伦理委员会批准并签署知情同意书后,采用整群随机抽样法获取调查样本。共发放问卷2864份,其中有效问卷2642份,占92.25%。以特质怒部分分值>x+s为高特质怒、分值 2.挑选基因多态性位点
查阅相关文献,选择国外已有初步研究的色氨酸羟化酶(TPH)基因A218C(rs1800532)位点,儿茶酚胺氧位甲基转移酶(COMT)基因V158M(rs4680)位点,单胺氧化酶A(MAOA)基因30bp-uVNTR位点,做进一步研究；此外,还选取了上述三种神经递质代谢酶基因中较小且研究相对较少的MAOA基因,从人类基因组单体型图(HapMap)中选出能代表汉族人该基因SNP阳性信号的tag SNP,即rs5906597、rs2235186、rs1181275和rs5905613,同时还选取该基因中的一个功能性SNP位点rs58524323,做探索性的研究。
3.DNA提取
(1)标本的采集和处理
征得知情同意后,用负压采血管对合格受试者行静脉穿刺采血5ml (2% EDTA-Na2200μl抗凝),血样置-20℃冰箱保存,两周内提取DNA。
(2)DNA的提取方法
将-20℃低温冷冻保存的血样于室温水浴解冻,将600μl血样移入EP离心管,加入等体积红细胞裂解液,充分混匀后12000转/min离心,吸去含有裂解红细胞的上清液。加入白细胞裂解液450μl,打碎沉淀物。
向离心管中加入10%SDS40μl,充分混匀10min,再加入蛋白酶K10μl,上下颠转离心管轻柔混匀,置于37℃水浴过夜。
将溶液冷却至室温,加入等体积Tris饱和酚,将离心管置于旋转器上充分混匀10min,使两相形成乳浊液；混匀后12000转/min离心5min,用宽口移液管吸取上层水相层移至新的离心管中,加入等体积的酚/氯仿(体积比1/1)500μl,充分混匀使两相形成乳浊液；混匀后10000转/min离心5min,用宽口移液管吸取上层水相层移至新的离心管中,加入等体积的氯仿,再次充分混匀,而后12000转/min离心10min。
用宽口移液管将水相转移至新的离心管,在水相中加入1/10体积3mol/L的NaCl和800μ1冷无水乙醇,颠转离心管轻柔混匀,沉淀DNA,12000转/min离心5min。用70%冷乙醇重悬DNA沉淀,12000转/min离心10min,弃去上清,反复洗涤三次,室温干燥后溶于适量灭菌水中,-20℃保存备用。
4.基因分型
(1)PCR扩增目的片段
以基因组DNA为模板,分别使用下列各对引物PCR扩增目的片段。引物设计所需的基因组DNA序列均来自美国国家生物信息中心(http://www.ncbi.nlm.nih.gov/)。所有引物序列均采用Primer Premier 5.0软件设计。引物的设计与合成由上海捷瑞生物工程有限公司完成。待测多态性位点PCR扩增引物的名称、序列(5'-3')、扩增产物长度如下。
rs1800532：上游引物F GCATTTAGAATGGTACCTGGC下游引物R CACCACTCGATGCAACATTTG扩增的产物长度为231bp
rs4680：上游引物F TACTGTGGCTACTCAGCTGTG下游引物R TTCAGTGAACGTGGTGTGAAC扩增的产物长度为240bp
rs5906957：上游引物F CAGATTACTAGAGTAGGCTCC下游引物R GGTTACAGAGGTTATTGGCAG扩增的产物长度为230bp
rs2235186：上游引物F AGAATGAAGCTGGAGAGAGAG下游引物R TTGAATAGGAGGTCACCTGTC扩增的产物长度为233bp
rs1181275：上游引物F CTTCACTTCCATTCCTACTCC下游引物R AAGTAGTAAAATGAAGGTATG扩增的产物长度为190bp
rs5905613：上游引物F CCACAATAGATAACCTTGGGC下游引物R CCTGGGCCAAAAATGCTATTC扩增的产物长度为222bp
rs58524323：上游引物F CATGACATTCTCTGACTCCTG下游引物R CAGAACAGACACATACACACC扩增的产物长度为229bp
MAOA基因30bp-uVNTR:上游引物F FAM-AGCACGCGTGCCTCAGCCTCCTTCCCCGGC下游引物R CCGAGATTCGGCGGGCCCTCCGCCTTGCGC扩增的产物长度为140-230bp
PCR反应体系：模板DNAlμl,10XPCR缓冲液1.5μl, MgCl2 (25mM) 1.5μl, dNTP (10mM) 0.3μ1, Taq酶1.25U,引物各0.25μl,使用去离子水补足体积至25μl。PCR反应条件：94℃预变性2分钟；94℃变性15秒、60℃退火15秒、72℃延伸30秒共35个循环；72℃延伸3分钟。
扩增完成后,1.2%琼脂糖凝胶电泳获得目的核苷酸片段。
(2)SNP位点连接酶检测反应
针对每个位点设计分别用于识别两种不同碱基的左端探针(长度相差3bp),以及带荧光(FAM)的右端共用探针,终产物长度差别即为左端探针的长度差别。LDR探针由上海捷瑞生物工程有限公司设计、合成,探针名称、序列(5'-3')、连接产物长度如下。
rs 1800532左端探针TA:TATTAATTGACAACCTATTACGTGA左端探针TC:TTTTATTAATTGACAACCTATTACGTGC右端公用探针：P-TAGCTGCTATTCTGAGCATAGGGAA-FAM连接产物的大小分别为：50/A和53/C；
rs4680左端探针TA:TTTTCAGCGGATGGTGGATTTCGCAGGCA左端探针TG:TTTTTTTCAGCGGATGGTGGATTTCGCAGGCG右端公用探针：P-TGAAGGACAAGGTGTGCATGCCTGATTT-FAM连接产物的大小分别为：57/A和60/G；
rs5906957左端探针TA:TTTTTTTTTCAGATTTTAGCATTTCCCTCCTCA左端探针TG:TTTTTTTTTTTTCAGATTTTAGCATTTCCCTCCTCG右端公用探针：P-AGACCTTCCAACGGCTCCCCTTCTCTTTTTT-FAM连接产物的大小分别为：64/A和67/G；
rs2235186左端探针TC:TCAGAAAGAAAGGGCAGCTCTTAAG左端探针TT:TTTTCAGAAAGAAAGGGCAGCTCTTAAA右端公用探针：P-ATAAACAGCTGTAACCTGATCATTC-FAM连接产物的大小分别为：50/C和53/T；
rs1181275左端探针TC:TTTTCATTTTCATTCATTTCTCCTTATAC左端探针TT:TTTTTTTCATTTTCATTCATTTCTCCTTATAT右端公用探针：P-GATTTATCCTTCCTATATATTTTTGTTT-FAM连接产物的大小分别为：57/C和60/T；
rs5905613左端探针TC:TTTTTTTTTACCAAATTCCTCACTATCACAGGC左端探针TT:TTTTTTTTTTTTACCAAATTCCTCACTATCACAGGT右端公用探针：P-TGTACCATTTGTACTTGAGCCAGCATTTTTT-FAM连接产物的大小分别为：64/C和67/T
rs58524323左端探针TA:TTTTTTTTTTTTATATTCACAAAAAGATAAGCTAACT左端探针TG:TTTTTTTTTTTTTTTATATTCACAAAAAGATAAGCTAACC右端公用探针：P-GCCTAGCAGTCCTGTTCATAGAACATTTTTTTTT-FAM连接产物的大小分别为：71/A和74/G
10μl连接体系为：PCR产物3μl、10×Taq DNA ligase buffer 1μl、Taq DNA ligase5U,特定LDR探针各0.1pmol,去离子水补足体积至10μL。连接反应参数：94℃变性30秒、60℃退火并连接3分钟,循环20次。反应结束后,4℃保存待用。
(3)反应产物的扫描和结果的读取
分别取1μl上述七个SNP多态性位点的连接反应产物及VNTR多态性位点的PCR产物,加10μl上样buffer(已混入Marker),95℃变性3分钟,立即冰水浴。反应产物经ABI 3730XL测序仪扫描,根据目的峰与Marker的位置差距来读取结果。
5.统计分析
数据资料采用SPSS13.0进行统计分析。定性资料采用频率指标描述,组间比较采用卡方检验；不同基因型的得分采用均数加减标准差(x±s)描述,并进行单因素方差分析；相关分析采用线性相关,并计算Pearson相关系数。所有的统计检验均采用双侧检验,检验水准a=0.05,P<0.05被认为差异有统计学意义。
结果：
1.高、低特质怒组8个多态性位点基因型和等位基因频率分布比较：差异均无统计学意义(P>0.05)。
2.8个基因多态性位点各基因型组怒的表达部分得分比较：高特质怒组中,对于TPH基因A218C位点各基因型组,发怒(AX-O)得分差异有统计学意义(F=3.252,P=0.041),女性怒的表达(AX)得分差异有统计学意义(F=6.668,P=0.002),男性郁怒(AX-I)得分差异有统计学意义(F=4.693,P=0.012)；其余各基因多态性位点不同基因型组怒的表达、发怒、郁怒的得分差异无统计学意义(P>0.05)。低特质怒组中,TPH基因A218C位点各基因型组郁怒得分差异有统计学意义(F=3.113,P=0.046)；其余各基因多态性位点不同基因型组怒的表达、发怒、郁怒的得分差异无统计学意义(P>0.05)。
3.8个基因多态性位点各基因型组怒的控制部分得分比较：高特质怒组中,男性TPH基因A218C位点各基因型组控制发怒(AC-O)得分差异有统计学意义(F=3.551,P=0.034),其余各基因多态性位点不同基因型受试者怒的控制(AC)、控制发怒、控制郁怒(AC-I)的得分差异无统计学意义(P>0.05)。低特质怒组中,对于TPH基因A218C位点各基因型组,怒的控制得分差异有统计学意义(F=5.227,P=0.006),控制发怒的得分差异有统计学意义(F=5.943,P=0.003),控制郁怒的得分差异有统计学意义(F=4.104,P=0.018),女性控制发怒的得分差异有统计学意义(F=3.527,P=0.032)；对于MAOA基因rs2235186位点,女性各基因型组控制发怒的得分差异有统计学意义(F=3.383,P=0.037)；其余各基因多态性位点不同基因型受试者怒的控制、控制发怒、控制郁怒的得分差异无统计学意义(P>0.05)。
4.高、低特质怒组特质怒、怒的表达、怒的控制间的相关性：两组无论是否按男女分层,特质怒与发怒均正相关(r=0.493,P<0.01。r=0.377,P<0.01),怒的表达与发怒及郁怒均正相关(r=0.521,P<0.01；r=0.751,P<0.01。r=0.393,P<0.01：r=0.885,P<0.01),怒的控制与控制发怒、控制郁怒均正相关(r=0.940,P<0.01：r=0.952,P<0.01。r=0.952,P<0.01；r=0.954,P<0.01),控制发怒与控制郁怒均正相关(r=0.791,P<0.0l。r=0.816,P<0.01)；而发怒与怒的控制、控制发怒、控制郁怒均负相关(r=-0.336,P<0.01；r=-0.391,P<0.01；r=-0.252,P<0.01。r=-0.305,P<0.01；r=-0.351,P<0.01；r=-0.231,P<0.01)。
结论：
1.TPH基因A218C多态性与我国正常大学生中高特质怒者下列愤怒情志特质有关：发怒特质,女性怒的表达特质,男性的郁怒特质及控制发怒特质；该位点多态性还与我国正常大学生中低特质怒者下列愤怒情志特质有关：郁怒特质,怒的控制特质,控制发怒特质,控制郁怒特质及女性的控制发怒特质。
2. MAOA基因tag SNP rs2235186多态性与我国正常大学生中低特质怒女性的控制发怒特质有关。
3. COMT基因的V158M位点及MAOA基因的30bp-uVNTR、rs1181275、rs5906957.rs5905613和rs58524323多态性与我国正常大学生的愤怒情志特质无关。
4.无论是否按男女进行分层,高、低特质怒组愤怒情志特质各维度间均存在如下相关关系：特质怒与发怒特质正相关,怒的表达特质与发怒特质及郁怒特质正相关,怒的控制特质与控制发怒特质、控制郁怒特质正相关,控制发怒特质与控制郁怒特质正相关；而发怒特质与怒的控制特质、控制发怒特质、控制郁怒特质负相关。
Objective:This paper attempts to investigate the relationships between anger emotion trait and neurotransmitter metabolic enzymes genetic polymorphisms, and analyze correlations among the dimensions of anger emotion trait。
Methods:
1. STAXI-2 questionnaire inquiry
Subjects are normal college students who come from Henan University of Traditional Chinese Medicine. After the ethics committee approved and signed the informed consent forms, we use cluster random sampling method to collect survey samples. A total of 2864 questionnaires were issued, in which 2642 questionnaires were valid, accounting for 92.25%. According to the trait anger scale, We define scores> x+s as the high trait anger, scores< x-s as the low trait anger.Thus there are 364 high trait anger people and 473 low trait anger people. According to this study's sample size required, we should take 236 people of the high trait anger, whose scores range from high to low, take 236 people of the low trait anger, whose scores range from low to high. By concentrating of blood, extracting DNA and genotyping and other steps, we exclude those who did not participate in blood concentrating and the lost blood samples in the extraction of DNA, and eventually we proceed with the statistical analysis of the data of 225 high trait anger people and 221 low trait anger people.
2. Selection of gene polymorphisms sites
In the light of relevant literature, we select tryptophan hydroxylase (TPH) gene A218C (rs1800532) sites, catecholamine-O-methyltransferase (COMT) gene V158M (rs4680) sites and monoamine oxidase A (MAOA) Gene 30bp-uVNTR sites for further research, which have been preliminarily studied by foreign countries. In addition, we select MAOA gene which the smallest gene and lest studied gene in the three neurotransmitter metabolism gene, and select tag SNP from the Haplotype map of human genome(HapMap) which are rs5906597, rs2235186, rs1181275 and rs5905613 whose tag SNPs can represent Han positive signal of the MAOA gene's SNPs. At the same time, we choose a functional SNP of MAOA gene, which is the site rs58524323 to proceed with exploratory research.
3. DNA extraction
(1) specimen collection and processing
After the informed consent forms were approved and signed, we used vacuum blood collection to needle eligible subjects for vein blood 5ml (2% EDTA-Na 2200μl anticoagulant), and then we stored the blood samples at -20℃in the refrigerator for two weeks.
(2) DNA extraction method
We unfreezed -20℃cryopreservation blood samples at room temperature water, and put 600μl blood samples into the EP tube, and added equal volume of erythrocyte lysis buffer, and finally used 12 000 circle/min after mix well for centrifugation of blood samples. These procedures can ensure the absorption the supernatant which include lysis red blood cells. At last, we added leukocyte lysis buffer 450μl and broke sediments.
Adding 40μl 10% SDS to centrifuge tube, we made the full mixing for 10min, and then added protease K10μl, and gently shaked them up by transferring centrifuge tube, and eventually bathed them in 37℃water overnight.
We let the solution cool off, and the solution graduated into to room temperature. We added an equal volume of Tris saturated phenol, and placed the tube on the rotator for full mix 10min, so that the formation of two-phase emulsion can be achieved. Furthermore, we centrifugated it for 5min by 12 OOOcircle/min with a wide-bore pipette drawing the upper layer of water phase to a new centrifuge tube, added an equal volume of phenol/chloroform (volume ratio 1/1) 500μl, and mixed well to form a two-phase emulsion. And then we centrifugated it for 5min by 10 000 circle/min with wide-bore pipette drawing the upper aqueous layer to a new centrifuge tube, and added an equal volume of chloroform for a thorough mixing, and then centrifugated 10min by 12 000 circle/min.
We transfered the water phase to new centrifuge tubes with a wide mouth pipette, and added 1/10 volume 3mol/L of NaCl and 800μl cold ethanol to the aqueous phase, and gently mixed them by reversing the centrifuge tube. Furthermore, we got precipitated DNA to 12000 circle/min for 5min's centrifugation. And then we used 70% cold ethanol to re-suspend DNA precipitation, and centrifugated it for 10min by 12 000circle/min, and finally discarded supernatant and repeated washing three times. The DNA precipitation should be dried and dissolved in appropriate amount of sterile water, storing at -20℃for standby application.
4. Genotyping
(1) PCR amplified fragment
Genomic DNA as template, respectively using the following primers PCR amplified purpose fragments. Genomic DNA sequence required by Primer design were from the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/). All primers were designed using Primer Premier 5.0 software. Primer Design and Synthesis were accomplished by Biological Engineering limited company of ShangHai Jierui. The name, sequence (5' -3'), amplified product length of wait for detect polymorphic locus' PCR amplification primer are as follows.
rs1800532:upstream primer F GCATTTAGAATGGTACCTGGC downstream primer R CACCACTCGATGCAACATTTG Amplified product length 231bp
rs4680:upstream primer F TACTGTGGCTACTCAGCTGTG downstream primer R TTCAGTGAACGTGGTGTGAAC Amplified product length 240bp
rs5906957:upstream primer F CAGATTACTAGAGTAGGCTCC downstream primer R GGTTACAGAGGTTATTGGCAG Amplified product length 230bp
rs2235186:upstream primer F AGAATGAAGCTGGAGAGAGAG downstream primer R TTGAATAGGAGGTCACCTGTC Amplified product length 233bp
rs1181275:upstream primer F CTTCACTTCCATTCCTACTCC downstream primer R AAGTAGTAAAATGAAGGTATG Amplified product length 190bp
rs5905613:upstream primer F CCACAATAGATAACCTTGGGC downstream primer R CCTGGGCCAAAAATGCTATTC Amplified product length 222bp
rs58524323:upstream primer F CATGACATTCTCTGACTCCTG downstream primer R CAGAACAGACACATACACACC Amplified product length 229bp
MAOA基因30bp-uVNTR: upstream primer F FAM-AGCACGCGTGCCTCAGCCTCCTTCCCCGGC downstream primer R CCGAGATTCGGCGGGCCCTCCGCCTTGCGC Amplified product length 140-230bp
PCR reaction system:template DNA1μl,10 X PCR buffer 1.5μl, MgC12 (25mM) 1.5μl, dNTP (10mM) 0.3μl, Taq enzyme 1.25U, each primer 0.25μl, make up the volume with deionized water to 25μl. PCR reaction conditions:94℃fore-denaturation for 2 minutes; 94℃denaturation for 15 seconds,60℃annealing for 15 seconds,72℃extend for 30 seconds,35 cycles; 72℃extend for 3 minutes.
When amplification was accomplished, use 1.2% agarose gel electrophoresis to obtain the purpose of DNA fragment.
(2) SNP loci ligase detection reaction
Design two left end of the probe(length difference 3bp) for each locus which were used to identify two different bases, and design right end of common probe which with fluorescence (FAM) for each locus, the difference length of the end product were the difference length between the left end of the probe. LDR probe were designed by Biological Engineering limited company of ShangHai Jierui.The name, sequence (5' -3')and product length of the probes are as follows.
rs1800532 Left end of the probe TA:TATTAATTGACAACCTATTACGTGA Left end of the probe TC:TTTTATTAATTGACAACCTATTACGTGC Right common probe:P-TAGCTGCTATTCTGAGCATAGGGAA-FAM The size of the product are connected:50/A and 53/C;
rs4680 Left end of the probe TA:TTTTCAGCGGATGGTGGATTTCGCAGGCA Left end of the probe TG:TTTTTTTCAGCGGATGGTGGATTTCGCAGGCG Right common probe:P-TGAAGGACAAGGTGTGCATGCCTGATTT-FAM The size of the product are connected:57/A和60/G;
rs5906957 Left end of the probe TA:TTTTTTTTTCAGATTTTAGCATTTCCCTCCTCA Left end of the probe TG:TTTTTTTTTTTTCAGATTTTAGCATTTCCCTCCTCG Right common probe:P-AGACCTTCCAACGGCTCCCCTTCTCTTTTTT-FAM The size of the product are connected:64/A和67/G;
rs2235186 Left end of the probe TC:TCAGAAAGAAAGGGCAGCTCTTAAG Left end of the probe TT:TTTTCAGAAAGAAAGGGCAGCTCTTAAA Right common probe:P-ATAAACAGCTGTAACCTGATCATTC-FAM The size of the product are connected:50/C和53/T;
rs1181275 Left end of the probe TC:TTTTCATTTTCATTCATTTCTCCTTATAC Left end of the probe TT:TTTTTTTCATTTTCATTCATTTCTCCTTATAT Right common probe:P-GATTTATCCTTCCTATATATTTTTGTTT-FAM The size of the product are connected:57/C和60/T;
rs5905613 Left end of the probe TC:TTTTTTTTTACCAAATTCCTCACTATCACAGGC Left end of the probe TT:TTTTTTTTTTTTACCAAATTCCTCACTATCACAGGT Right common probe:P-TGTACCATTTGTACTTGAGCCAGCATTTTTT-FAM The size of the product are connected:64/C和67/T
rs58524323 Left end of the probe TA:TTTTTTTTTTTTATATTCACAAAAAGATAAGCTAACT Left end of the probe TG:TTTTTTTTTTTTTTTATATTCACAAAAAGATAAGCTAACC Right common probe:P-GCCTAGCAGTCCTGTTCATAGAACATTTTTTTTT-FAM The size of the product are connected:71/A和74/G
10μl connection system:PCR product 3μl,10×Taq DNA ligase buffer 1μl, Taq DNA ligase5U, every specific LDR probe 0.1pmol, make up the volume with deionized water to 10μL. Connect reaction parameters:94℃denaturation for 30 seconds,60℃annealing and connect 3 minutes,20 cycles. When reaction was accomplished,4℃stored for later use.
(3) Scanning the reaction products and reading the results
The seven SNP polymorphisms connection reaction products and VNTR polymorphisms' PCR product were taken 1μl, add 10μl of sample buffer (has already mixed with Marker),95℃denaturation 3 minutes, ice water bath immediately. scan reaction products by ABI 3730XL sequenator, according to the gap between position of the purpose peak and the Marker to read the results.
5. Statistical analysis
Data were analyzed by SPSS13.0. qualitative data described by the frequency index, group comparison using chi-square test; the score of different genotypes described by the mean score plus or minus standard deviation (x±s), and carry out the single factor analysis of variance; correlation analysis using linear correlation, Pearson correlation coefficients were calculated. All statistical tests were used two-sided test, test level a=0.05, P<0.05 was considered statistically significant difference.
Results:
1. We make a comparison of frequency distribution of genotype and allele of 8 gene polymorphic locus of high and low trait anger groups:the difference was not statistically significant (P>0.05).
2. The analysis of scores of the anger expression of 8 gene polymorphism locus'genotype groups shows:in high trait anger group, with regard to each genotype of the TPH gene A218C locus, the scores of anger expression-out are significantly (F=1=3.252,P=0.041), female scores of anger expression are significantly (F=6.668, P=0.002), male scores of anger expression-in are significantly (F=4.693, P=0.012); In terms of genotype groups of the rest gene polymorphisms locus, anger expression, anger expression-out and anger expression-in are no significant difference in scores (P>0.05). In low trait anger group, with regard to each genotype of the TPH gene A218C locus, the scores of anger expression-in are significantly (F=3.113, P=0.046); According to genotype groups of the rest gene polymorphisms locus, anger expression, anger expression-out and anger expression-in are no significant difference in scores (P>0.05).
3. The analysis of scores of the anger control of 8 gene polymorphism locus' genotype groups shows:in high trait anger group, at genotypes of the TPH gene A218C locus, male scores of anger control-out are significantly (F =3.551,P=0.034), but in terms of the rest gene polymorphisms locus' different genotype groups, anger control, anger control-out and anger control-in are no significant difference in scores (P>0.05). In low trait anger group, at genotypes of the TPH gene A218C locus, and the scores of anger control are significantly (F=5.227,P=0.006), so are the scores of anger control-out (F=5.943, P=0.003) and the scores of anger control-in (F=4.104, P=0.018) and female scores of anger control-out (F=3.527,P=0.032). At genotypes of locus rs2235186 of MAOA gene, female scores of anger control-out are significantly (F=3.383,P=0.037), but in terms of the rest gene polymorphisms locus' different genotype groups, anger control, anger control-out and anger control-in are no significant difference in scores (P >0.05).
4. The correlations between trait anger, anger expression and anger control in high and low trait anger groups tell us that trait anger and anger expression-out are positively correlated 0=0.493, P<0.01。r=0.377, P< 0.01) Whether the two groups are stratified by sex; and anger expression and anger expression-out, anger expression and anger expression-in are correlated (r=0.521,P<0.01; r=0.751, P<0.01。r=0.393,P<0.01; r=0.885, P<0.01). In addition, anger control and anger control-out, anger control and anger control-in are positively correlated (r=0.940,P<0.01; r=0.952, P<0.01。r=0.952,P<0.01; r=0.954,P<0.01); and anger control-out and anger control-in are positively correlated (r=0.791,P<0.01。r=0.816,P<0.01), while anger expression-out and anger control, anger expression-out and anger control-out, anger expression-out and anger control-in are negatively correlated (r=-0.336, P<0.01; r=-0.391, P<0.01; r=-0.252, P<0.01。r=-0.305,P<0.01; r=-0.351,P<0.01; r=-0.231,P<0.01)
Conclusion:
1. TPH gene A218C polymorphism is related with the following anger emotion trait of normal college students of the high trait anger in our country:anger expression-out traits, female anger expression traits, male anger expression-in traits and anger control-out traits. The polymorphism is concerned with the following anger emotion trait of normal college students of the low trait anger in our country:anger expression-in traits, anger control traits, anger control-out traits, anger control-in traits and female anger control-out traits.
2. MAOA gene tag SNP rs2235186 is related with female anger control-out traits of normal college students of the low trait anger in our country.
3. COMT gene V158M locus polymorphism and MAOA gene 30bp-uVNTR, rs1181275, rs5906957, rs5905613 and rs58524323 do not have relations with anger emotion traits of normal college students in our country.
4. The following relationships can be found at either men or women in various dimensions of anger emotion traits of high and low trait anger groups: trait anger and anger expression-out trait are positively correlated; anger expression trait and anger expression-out trait, anger expression trait and anger expression-in trait are positively correlated, anger control trait and anger control-out trait, anger control trait and anger control-in trait are positively correlated, anger control-out trait and anger control-in trait are positively correlated. While anger expression-out trait and anger control trait, anger expression-out trait and anger control-out trait, anger expression-out trait and anger control-in trait are negatively correlated.
方法：
1.状态-特质怒表达量表Ⅱ问卷调查
以河南中医学院在校正常大学生为调查对象,经伦理委员会批准并签署知情同意书后,采用整群随机抽样法获取调查样本。共发放问卷2864份,其中有效问卷2642份,占92.25%。以特质怒部分分值>x+s为高特质怒、分值
查阅相关文献,选择国外已有初步研究的色氨酸羟化酶(TPH)基因A218C(rs1800532)位点,儿茶酚胺氧位甲基转移酶(COMT)基因V158M(rs4680)位点,单胺氧化酶A(MAOA)基因30bp-uVNTR位点,做进一步研究；此外,还选取了上述三种神经递质代谢酶基因中较小且研究相对较少的MAOA基因,从人类基因组单体型图(HapMap)中选出能代表汉族人该基因SNP阳性信号的tag SNP,即rs5906597、rs2235186、rs1181275和rs5905613,同时还选取该基因中的一个功能性SNP位点rs58524323,做探索性的研究。
3.DNA提取
(1)标本的采集和处理
征得知情同意后,用负压采血管对合格受试者行静脉穿刺采血5ml (2% EDTA-Na2200μl抗凝),血样置-20℃冰箱保存,两周内提取DNA。
(2)DNA的提取方法
将-20℃低温冷冻保存的血样于室温水浴解冻,将600μl血样移入EP离心管,加入等体积红细胞裂解液,充分混匀后12000转/min离心,吸去含有裂解红细胞的上清液。加入白细胞裂解液450μl,打碎沉淀物。
向离心管中加入10%SDS40μl,充分混匀10min,再加入蛋白酶K10μl,上下颠转离心管轻柔混匀,置于37℃水浴过夜。
将溶液冷却至室温,加入等体积Tris饱和酚,将离心管置于旋转器上充分混匀10min,使两相形成乳浊液；混匀后12000转/min离心5min,用宽口移液管吸取上层水相层移至新的离心管中,加入等体积的酚/氯仿(体积比1/1)500μl,充分混匀使两相形成乳浊液；混匀后10000转/min离心5min,用宽口移液管吸取上层水相层移至新的离心管中,加入等体积的氯仿,再次充分混匀,而后12000转/min离心10min。
用宽口移液管将水相转移至新的离心管,在水相中加入1/10体积3mol/L的NaCl和800μ1冷无水乙醇,颠转离心管轻柔混匀,沉淀DNA,12000转/min离心5min。用70%冷乙醇重悬DNA沉淀,12000转/min离心10min,弃去上清,反复洗涤三次,室温干燥后溶于适量灭菌水中,-20℃保存备用。
4.基因分型
(1)PCR扩增目的片段
以基因组DNA为模板,分别使用下列各对引物PCR扩增目的片段。引物设计所需的基因组DNA序列均来自美国国家生物信息中心(http://www.ncbi.nlm.nih.gov/)。所有引物序列均采用Primer Premier 5.0软件设计。引物的设计与合成由上海捷瑞生物工程有限公司完成。待测多态性位点PCR扩增引物的名称、序列(5'-3')、扩增产物长度如下。
rs1800532：上游引物F GCATTTAGAATGGTACCTGGC下游引物R CACCACTCGATGCAACATTTG扩增的产物长度为231bp
rs4680：上游引物F TACTGTGGCTACTCAGCTGTG下游引物R TTCAGTGAACGTGGTGTGAAC扩增的产物长度为240bp
rs5906957：上游引物F CAGATTACTAGAGTAGGCTCC下游引物R GGTTACAGAGGTTATTGGCAG扩增的产物长度为230bp
rs2235186：上游引物F AGAATGAAGCTGGAGAGAGAG下游引物R TTGAATAGGAGGTCACCTGTC扩增的产物长度为233bp
rs1181275：上游引物F CTTCACTTCCATTCCTACTCC下游引物R AAGTAGTAAAATGAAGGTATG扩增的产物长度为190bp
rs5905613：上游引物F CCACAATAGATAACCTTGGGC下游引物R CCTGGGCCAAAAATGCTATTC扩增的产物长度为222bp
rs58524323：上游引物F CATGACATTCTCTGACTCCTG下游引物R CAGAACAGACACATACACACC扩增的产物长度为229bp
MAOA基因30bp-uVNTR:上游引物F FAM-AGCACGCGTGCCTCAGCCTCCTTCCCCGGC下游引物R CCGAGATTCGGCGGGCCCTCCGCCTTGCGC扩增的产物长度为140-230bp
PCR反应体系：模板DNAlμl,10XPCR缓冲液1.5μl, MgCl2 (25mM) 1.5μl, dNTP (10mM) 0.3μ1, Taq酶1.25U,引物各0.25μl,使用去离子水补足体积至25μl。PCR反应条件：94℃预变性2分钟；94℃变性15秒、60℃退火15秒、72℃延伸30秒共35个循环；72℃延伸3分钟。
扩增完成后,1.2%琼脂糖凝胶电泳获得目的核苷酸片段。
(2)SNP位点连接酶检测反应
针对每个位点设计分别用于识别两种不同碱基的左端探针(长度相差3bp),以及带荧光(FAM)的右端共用探针,终产物长度差别即为左端探针的长度差别。LDR探针由上海捷瑞生物工程有限公司设计、合成,探针名称、序列(5'-3')、连接产物长度如下。
rs 1800532左端探针TA:TATTAATTGACAACCTATTACGTGA左端探针TC:TTTTATTAATTGACAACCTATTACGTGC右端公用探针：P-TAGCTGCTATTCTGAGCATAGGGAA-FAM连接产物的大小分别为：50/A和53/C；
rs4680左端探针TA:TTTTCAGCGGATGGTGGATTTCGCAGGCA左端探针TG:TTTTTTTCAGCGGATGGTGGATTTCGCAGGCG右端公用探针：P-TGAAGGACAAGGTGTGCATGCCTGATTT-FAM连接产物的大小分别为：57/A和60/G；
rs5906957左端探针TA:TTTTTTTTTCAGATTTTAGCATTTCCCTCCTCA左端探针TG:TTTTTTTTTTTTCAGATTTTAGCATTTCCCTCCTCG右端公用探针：P-AGACCTTCCAACGGCTCCCCTTCTCTTTTTT-FAM连接产物的大小分别为：64/A和67/G；
rs2235186左端探针TC:TCAGAAAGAAAGGGCAGCTCTTAAG左端探针TT:TTTTCAGAAAGAAAGGGCAGCTCTTAAA右端公用探针：P-ATAAACAGCTGTAACCTGATCATTC-FAM连接产物的大小分别为：50/C和53/T；
rs1181275左端探针TC:TTTTCATTTTCATTCATTTCTCCTTATAC左端探针TT:TTTTTTTCATTTTCATTCATTTCTCCTTATAT右端公用探针：P-GATTTATCCTTCCTATATATTTTTGTTT-FAM连接产物的大小分别为：57/C和60/T；
rs5905613左端探针TC:TTTTTTTTTACCAAATTCCTCACTATCACAGGC左端探针TT:TTTTTTTTTTTTACCAAATTCCTCACTATCACAGGT右端公用探针：P-TGTACCATTTGTACTTGAGCCAGCATTTTTT-FAM连接产物的大小分别为：64/C和67/T
rs58524323左端探针TA:TTTTTTTTTTTTATATTCACAAAAAGATAAGCTAACT左端探针TG:TTTTTTTTTTTTTTTATATTCACAAAAAGATAAGCTAACC右端公用探针：P-GCCTAGCAGTCCTGTTCATAGAACATTTTTTTTT-FAM连接产物的大小分别为：71/A和74/G
10μl连接体系为：PCR产物3μl、10×Taq DNA ligase buffer 1μl、Taq DNA ligase5U,特定LDR探针各0.1pmol,去离子水补足体积至10μL。连接反应参数：94℃变性30秒、60℃退火并连接3分钟,循环20次。反应结束后,4℃保存待用。
(3)反应产物的扫描和结果的读取
分别取1μl上述七个SNP多态性位点的连接反应产物及VNTR多态性位点的PCR产物,加10μl上样buffer(已混入Marker),95℃变性3分钟,立即冰水浴。反应产物经ABI 3730XL测序仪扫描,根据目的峰与Marker的位置差距来读取结果。
5.统计分析
数据资料采用SPSS13.0进行统计分析。定性资料采用频率指标描述,组间比较采用卡方检验；不同基因型的得分采用均数加减标准差(x±s)描述,并进行单因素方差分析；相关分析采用线性相关,并计算Pearson相关系数。所有的统计检验均采用双侧检验,检验水准a=0.05,P<0.05被认为差异有统计学意义。
结果：
1.高、低特质怒组8个多态性位点基因型和等位基因频率分布比较：差异均无统计学意义(P>0.05)。
2.8个基因多态性位点各基因型组怒的表达部分得分比较：高特质怒组中,对于TPH基因A218C位点各基因型组,发怒(AX-O)得分差异有统计学意义(F=3.252,P=0.041),女性怒的表达(AX)得分差异有统计学意义(F=6.668,P=0.002),男性郁怒(AX-I)得分差异有统计学意义(F=4.693,P=0.012)；其余各基因多态性位点不同基因型组怒的表达、发怒、郁怒的得分差异无统计学意义(P>0.05)。低特质怒组中,TPH基因A218C位点各基因型组郁怒得分差异有统计学意义(F=3.113,P=0.046)；其余各基因多态性位点不同基因型组怒的表达、发怒、郁怒的得分差异无统计学意义(P>0.05)。
3.8个基因多态性位点各基因型组怒的控制部分得分比较：高特质怒组中,男性TPH基因A218C位点各基因型组控制发怒(AC-O)得分差异有统计学意义(F=3.551,P=0.034),其余各基因多态性位点不同基因型受试者怒的控制(AC)、控制发怒、控制郁怒(AC-I)的得分差异无统计学意义(P>0.05)。低特质怒组中,对于TPH基因A218C位点各基因型组,怒的控制得分差异有统计学意义(F=5.227,P=0.006),控制发怒的得分差异有统计学意义(F=5.943,P=0.003),控制郁怒的得分差异有统计学意义(F=4.104,P=0.018),女性控制发怒的得分差异有统计学意义(F=3.527,P=0.032)；对于MAOA基因rs2235186位点,女性各基因型组控制发怒的得分差异有统计学意义(F=3.383,P=0.037)；其余各基因多态性位点不同基因型受试者怒的控制、控制发怒、控制郁怒的得分差异无统计学意义(P>0.05)。
4.高、低特质怒组特质怒、怒的表达、怒的控制间的相关性：两组无论是否按男女分层,特质怒与发怒均正相关(r=0.493,P<0.01。r=0.377,P<0.01),怒的表达与发怒及郁怒均正相关(r=0.521,P<0.01；r=0.751,P<0.01。r=0.393,P<0.01：r=0.885,P<0.01),怒的控制与控制发怒、控制郁怒均正相关(r=0.940,P<0.01：r=0.952,P<0.01。r=0.952,P<0.01；r=0.954,P<0.01),控制发怒与控制郁怒均正相关(r=0.791,P<0.0l。r=0.816,P<0.01)；而发怒与怒的控制、控制发怒、控制郁怒均负相关(r=-0.336,P<0.01；r=-0.391,P<0.01；r=-0.252,P<0.01。r=-0.305,P<0.01；r=-0.351,P<0.01；r=-0.231,P<0.01)。
结论：
1.TPH基因A218C多态性与我国正常大学生中高特质怒者下列愤怒情志特质有关：发怒特质,女性怒的表达特质,男性的郁怒特质及控制发怒特质；该位点多态性还与我国正常大学生中低特质怒者下列愤怒情志特质有关：郁怒特质,怒的控制特质,控制发怒特质,控制郁怒特质及女性的控制发怒特质。
2. MAOA基因tag SNP rs2235186多态性与我国正常大学生中低特质怒女性的控制发怒特质有关。
3. COMT基因的V158M位点及MAOA基因的30bp-uVNTR、rs1181275、rs5906957.rs5905613和rs58524323多态性与我国正常大学生的愤怒情志特质无关。
4.无论是否按男女进行分层,高、低特质怒组愤怒情志特质各维度间均存在如下相关关系：特质怒与发怒特质正相关,怒的表达特质与发怒特质及郁怒特质正相关,怒的控制特质与控制发怒特质、控制郁怒特质正相关,控制发怒特质与控制郁怒特质正相关；而发怒特质与怒的控制特质、控制发怒特质、控制郁怒特质负相关。
Objective:This paper attempts to investigate the relationships between anger emotion trait and neurotransmitter metabolic enzymes genetic polymorphisms, and analyze correlations among the dimensions of anger emotion trait。
Methods:
1. STAXI-2 questionnaire inquiry
Subjects are normal college students who come from Henan University of Traditional Chinese Medicine. After the ethics committee approved and signed the informed consent forms, we use cluster random sampling method to collect survey samples. A total of 2864 questionnaires were issued, in which 2642 questionnaires were valid, accounting for 92.25%. According to the trait anger scale, We define scores> x+s as the high trait anger, scores< x-s as the low trait anger.Thus there are 364 high trait anger people and 473 low trait anger people. According to this study's sample size required, we should take 236 people of the high trait anger, whose scores range from high to low, take 236 people of the low trait anger, whose scores range from low to high. By concentrating of blood, extracting DNA and genotyping and other steps, we exclude those who did not participate in blood concentrating and the lost blood samples in the extraction of DNA, and eventually we proceed with the statistical analysis of the data of 225 high trait anger people and 221 low trait anger people.
2. Selection of gene polymorphisms sites
In the light of relevant literature, we select tryptophan hydroxylase (TPH) gene A218C (rs1800532) sites, catecholamine-O-methyltransferase (COMT) gene V158M (rs4680) sites and monoamine oxidase A (MAOA) Gene 30bp-uVNTR sites for further research, which have been preliminarily studied by foreign countries. In addition, we select MAOA gene which the smallest gene and lest studied gene in the three neurotransmitter metabolism gene, and select tag SNP from the Haplotype map of human genome(HapMap) which are rs5906597, rs2235186, rs1181275 and rs5905613 whose tag SNPs can represent Han positive signal of the MAOA gene's SNPs. At the same time, we choose a functional SNP of MAOA gene, which is the site rs58524323 to proceed with exploratory research.
3. DNA extraction
(1) specimen collection and processing
After the informed consent forms were approved and signed, we used vacuum blood collection to needle eligible subjects for vein blood 5ml (2% EDTA-Na 2200μl anticoagulant), and then we stored the blood samples at -20℃in the refrigerator for two weeks.
(2) DNA extraction method
We unfreezed -20℃cryopreservation blood samples at room temperature water, and put 600μl blood samples into the EP tube, and added equal volume of erythrocyte lysis buffer, and finally used 12 000 circle/min after mix well for centrifugation of blood samples. These procedures can ensure the absorption the supernatant which include lysis red blood cells. At last, we added leukocyte lysis buffer 450μl and broke sediments.
Adding 40μl 10% SDS to centrifuge tube, we made the full mixing for 10min, and then added protease K10μl, and gently shaked them up by transferring centrifuge tube, and eventually bathed them in 37℃water overnight.
We let the solution cool off, and the solution graduated into to room temperature. We added an equal volume of Tris saturated phenol, and placed the tube on the rotator for full mix 10min, so that the formation of two-phase emulsion can be achieved. Furthermore, we centrifugated it for 5min by 12 OOOcircle/min with a wide-bore pipette drawing the upper layer of water phase to a new centrifuge tube, added an equal volume of phenol/chloroform (volume ratio 1/1) 500μl, and mixed well to form a two-phase emulsion. And then we centrifugated it for 5min by 10 000 circle/min with wide-bore pipette drawing the upper aqueous layer to a new centrifuge tube, and added an equal volume of chloroform for a thorough mixing, and then centrifugated 10min by 12 000 circle/min.
We transfered the water phase to new centrifuge tubes with a wide mouth pipette, and added 1/10 volume 3mol/L of NaCl and 800μl cold ethanol to the aqueous phase, and gently mixed them by reversing the centrifuge tube. Furthermore, we got precipitated DNA to 12000 circle/min for 5min's centrifugation. And then we used 70% cold ethanol to re-suspend DNA precipitation, and centrifugated it for 10min by 12 000circle/min, and finally discarded supernatant and repeated washing three times. The DNA precipitation should be dried and dissolved in appropriate amount of sterile water, storing at -20℃for standby application.
4. Genotyping
(1) PCR amplified fragment
Genomic DNA as template, respectively using the following primers PCR amplified purpose fragments. Genomic DNA sequence required by Primer design were from the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/). All primers were designed using Primer Premier 5.0 software. Primer Design and Synthesis were accomplished by Biological Engineering limited company of ShangHai Jierui. The name, sequence (5' -3'), amplified product length of wait for detect polymorphic locus' PCR amplification primer are as follows.
rs1800532:upstream primer F GCATTTAGAATGGTACCTGGC downstream primer R CACCACTCGATGCAACATTTG Amplified product length 231bp
rs4680:upstream primer F TACTGTGGCTACTCAGCTGTG downstream primer R TTCAGTGAACGTGGTGTGAAC Amplified product length 240bp
rs5906957:upstream primer F CAGATTACTAGAGTAGGCTCC downstream primer R GGTTACAGAGGTTATTGGCAG Amplified product length 230bp
rs2235186:upstream primer F AGAATGAAGCTGGAGAGAGAG downstream primer R TTGAATAGGAGGTCACCTGTC Amplified product length 233bp
rs1181275:upstream primer F CTTCACTTCCATTCCTACTCC downstream primer R AAGTAGTAAAATGAAGGTATG Amplified product length 190bp
rs5905613:upstream primer F CCACAATAGATAACCTTGGGC downstream primer R CCTGGGCCAAAAATGCTATTC Amplified product length 222bp
rs58524323:upstream primer F CATGACATTCTCTGACTCCTG downstream primer R CAGAACAGACACATACACACC Amplified product length 229bp
MAOA基因30bp-uVNTR: upstream primer F FAM-AGCACGCGTGCCTCAGCCTCCTTCCCCGGC downstream primer R CCGAGATTCGGCGGGCCCTCCGCCTTGCGC Amplified product length 140-230bp
PCR reaction system:template DNA1μl,10 X PCR buffer 1.5μl, MgC12 (25mM) 1.5μl, dNTP (10mM) 0.3μl, Taq enzyme 1.25U, each primer 0.25μl, make up the volume with deionized water to 25μl. PCR reaction conditions:94℃fore-denaturation for 2 minutes; 94℃denaturation for 15 seconds,60℃annealing for 15 seconds,72℃extend for 30 seconds,35 cycles; 72℃extend for 3 minutes.
When amplification was accomplished, use 1.2% agarose gel electrophoresis to obtain the purpose of DNA fragment.
(2) SNP loci ligase detection reaction
Design two left end of the probe(length difference 3bp) for each locus which were used to identify two different bases, and design right end of common probe which with fluorescence (FAM) for each locus, the difference length of the end product were the difference length between the left end of the probe. LDR probe were designed by Biological Engineering limited company of ShangHai Jierui.The name, sequence (5' -3')and product length of the probes are as follows.
rs1800532 Left end of the probe TA:TATTAATTGACAACCTATTACGTGA Left end of the probe TC:TTTTATTAATTGACAACCTATTACGTGC Right common probe:P-TAGCTGCTATTCTGAGCATAGGGAA-FAM The size of the product are connected:50/A and 53/C;
rs4680 Left end of the probe TA:TTTTCAGCGGATGGTGGATTTCGCAGGCA Left end of the probe TG:TTTTTTTCAGCGGATGGTGGATTTCGCAGGCG Right common probe:P-TGAAGGACAAGGTGTGCATGCCTGATTT-FAM The size of the product are connected:57/A和60/G;
rs5906957 Left end of the probe TA:TTTTTTTTTCAGATTTTAGCATTTCCCTCCTCA Left end of the probe TG:TTTTTTTTTTTTCAGATTTTAGCATTTCCCTCCTCG Right common probe:P-AGACCTTCCAACGGCTCCCCTTCTCTTTTTT-FAM The size of the product are connected:64/A和67/G;
rs2235186 Left end of the probe TC:TCAGAAAGAAAGGGCAGCTCTTAAG Left end of the probe TT:TTTTCAGAAAGAAAGGGCAGCTCTTAAA Right common probe:P-ATAAACAGCTGTAACCTGATCATTC-FAM The size of the product are connected:50/C和53/T;
rs1181275 Left end of the probe TC:TTTTCATTTTCATTCATTTCTCCTTATAC Left end of the probe TT:TTTTTTTCATTTTCATTCATTTCTCCTTATAT Right common probe:P-GATTTATCCTTCCTATATATTTTTGTTT-FAM The size of the product are connected:57/C和60/T;
rs5905613 Left end of the probe TC:TTTTTTTTTACCAAATTCCTCACTATCACAGGC Left end of the probe TT:TTTTTTTTTTTTACCAAATTCCTCACTATCACAGGT Right common probe:P-TGTACCATTTGTACTTGAGCCAGCATTTTTT-FAM The size of the product are connected:64/C和67/T
rs58524323 Left end of the probe TA:TTTTTTTTTTTTATATTCACAAAAAGATAAGCTAACT Left end of the probe TG:TTTTTTTTTTTTTTTATATTCACAAAAAGATAAGCTAACC Right common probe:P-GCCTAGCAGTCCTGTTCATAGAACATTTTTTTTT-FAM The size of the product are connected:71/A和74/G
10μl connection system:PCR product 3μl,10×Taq DNA ligase buffer 1μl, Taq DNA ligase5U, every specific LDR probe 0.1pmol, make up the volume with deionized water to 10μL. Connect reaction parameters:94℃denaturation for 30 seconds,60℃annealing and connect 3 minutes,20 cycles. When reaction was accomplished,4℃stored for later use.
(3) Scanning the reaction products and reading the results
The seven SNP polymorphisms connection reaction products and VNTR polymorphisms' PCR product were taken 1μl, add 10μl of sample buffer (has already mixed with Marker),95℃denaturation 3 minutes, ice water bath immediately. scan reaction products by ABI 3730XL sequenator, according to the gap between position of the purpose peak and the Marker to read the results.
5. Statistical analysis
Data were analyzed by SPSS13.0. qualitative data described by the frequency index, group comparison using chi-square test; the score of different genotypes described by the mean score plus or minus standard deviation (x±s), and carry out the single factor analysis of variance; correlation analysis using linear correlation, Pearson correlation coefficients were calculated. All statistical tests were used two-sided test, test level a=0.05, P<0.05 was considered statistically significant difference.
Results:
1. We make a comparison of frequency distribution of genotype and allele of 8 gene polymorphic locus of high and low trait anger groups:the difference was not statistically significant (P>0.05).
2. The analysis of scores of the anger expression of 8 gene polymorphism locus'genotype groups shows:in high trait anger group, with regard to each genotype of the TPH gene A218C locus, the scores of anger expression-out are significantly (F=1=3.252,P=0.041), female scores of anger expression are significantly (F=6.668, P=0.002), male scores of anger expression-in are significantly (F=4.693, P=0.012); In terms of genotype groups of the rest gene polymorphisms locus, anger expression, anger expression-out and anger expression-in are no significant difference in scores (P>0.05). In low trait anger group, with regard to each genotype of the TPH gene A218C locus, the scores of anger expression-in are significantly (F=3.113, P=0.046); According to genotype groups of the rest gene polymorphisms locus, anger expression, anger expression-out and anger expression-in are no significant difference in scores (P>0.05).
3. The analysis of scores of the anger control of 8 gene polymorphism locus' genotype groups shows:in high trait anger group, at genotypes of the TPH gene A218C locus, male scores of anger control-out are significantly (F =3.551,P=0.034), but in terms of the rest gene polymorphisms locus' different genotype groups, anger control, anger control-out and anger control-in are no significant difference in scores (P>0.05). In low trait anger group, at genotypes of the TPH gene A218C locus, and the scores of anger control are significantly (F=5.227,P=0.006), so are the scores of anger control-out (F=5.943, P=0.003) and the scores of anger control-in (F=4.104, P=0.018) and female scores of anger control-out (F=3.527,P=0.032). At genotypes of locus rs2235186 of MAOA gene, female scores of anger control-out are significantly (F=3.383,P=0.037), but in terms of the rest gene polymorphisms locus' different genotype groups, anger control, anger control-out and anger control-in are no significant difference in scores (P >0.05).
4. The correlations between trait anger, anger expression and anger control in high and low trait anger groups tell us that trait anger and anger expression-out are positively correlated 0=0.493, P<0.01。r=0.377, P< 0.01) Whether the two groups are stratified by sex; and anger expression and anger expression-out, anger expression and anger expression-in are correlated (r=0.521,P<0.01; r=0.751, P<0.01。r=0.393,P<0.01; r=0.885, P<0.01). In addition, anger control and anger control-out, anger control and anger control-in are positively correlated (r=0.940,P<0.01; r=0.952, P<0.01。r=0.952,P<0.01; r=0.954,P<0.01); and anger control-out and anger control-in are positively correlated (r=0.791,P<0.01。r=0.816,P<0.01), while anger expression-out and anger control, anger expression-out and anger control-out, anger expression-out and anger control-in are negatively correlated (r=-0.336, P<0.01; r=-0.391, P<0.01; r=-0.252, P<0.01。r=-0.305,P<0.01; r=-0.351,P<0.01; r=-0.231,P<0.01)
Conclusion:
1. TPH gene A218C polymorphism is related with the following anger emotion trait of normal college students of the high trait anger in our country:anger expression-out traits, female anger expression traits, male anger expression-in traits and anger control-out traits. The polymorphism is concerned with the following anger emotion trait of normal college students of the low trait anger in our country:anger expression-in traits, anger control traits, anger control-out traits, anger control-in traits and female anger control-out traits.
2. MAOA gene tag SNP rs2235186 is related with female anger control-out traits of normal college students of the low trait anger in our country.
3. COMT gene V158M locus polymorphism and MAOA gene 30bp-uVNTR, rs1181275, rs5906957, rs5905613 and rs58524323 do not have relations with anger emotion traits of normal college students in our country.
4. The following relationships can be found at either men or women in various dimensions of anger emotion traits of high and low trait anger groups: trait anger and anger expression-out trait are positively correlated; anger expression trait and anger expression-out trait, anger expression trait and anger expression-in trait are positively correlated, anger control trait and anger control-out trait, anger control trait and anger control-in trait are positively correlated, anger control-out trait and anger control-in trait are positively correlated. While anger expression-out trait and anger control trait, anger expression-out trait and anger control-out trait, anger expression-out trait and anger control-in trait are negatively correlated.
引文
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