甘肃东乡族、汉族5-羟色胺2C受体基因-759C/T多态性与2型糖尿病的相关性研究
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摘要
目的:探讨甘肃东乡族和汉族5-羟色胺2C受体(5-hydroxytryptamine 2C receptor,HTR2C)基因启动子区-759C/T多态性与2型糖尿病、肥胖的关系。
方法:采用病例对照的研究方法,应用聚合酶链反应(polymerase chain reaction,PCR)-连接酶检测反应(ligase detection reaction,LDR)方法检测东乡族100名2型糖尿病患者(T2DM组)和126名正常对照者(NC组)及汉族133名T2DM患者和135名正常对照者HTR2C基因-759C/T多态性。同时测量身高、体重、腰围、臀围,血压,计算体质量指数(BMI)=体重/身高~2(kg/m~2),腰臀比(WHR)=腰围/臀围。取空腹外周静脉血用全自动生化分析仪测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG),放射免疫法测定空腹胰岛素(FINS)。按稳态模式评估法计算胰岛素抵抗指数(HOMA-IR=FPG×FINS/22.5)。
结果:
1.东乡族T2DM组与NC组临床资料比较:T2DM组腰围、WHR、FPG、FINS、HOMA-IR、收缩压、舒张压、TG、LDL-C均高于NC组,差别有统计学意义(P＜0.05)。
2.汉族T2DM组与NC组临床资料比较:T2DM组腰围、WHR、FPG、FINS、HOMA-IR、收缩压、TG均高于NC组(P＜0.05),T2DM组HDL-C低于NC组,差别有统计学意义(P＜0.05)。
3.东乡族女性NC组和T2DM组CC、CT基因型频率分别为61%、39%和80.6%、19.4%,T2DM组CT基因型频率明显低于NC组(x~2=3.950,P=0.047,OR=0.378,95%CI0.145-0.987);两组C、T等位基因频率分布无统计学差异(x~2=3.210,P=0.073)。男性NC组和T2DM组C、T半合子型频率分布无统计学差异(x~2=0.122,P=0.727)。
4.汉族NC组与T2DM组间男性、女性各基因型频率及等位基因频率分布无统计学差异(P＞0.05)。
5.在正常对照人群,东乡族和汉族C、T等位基因频率分布差异无统计学意义(x~2=3.413,P=0.065)。两民族男性半合子型频率分布差异无统计学意义(x~2=0.367,P=0.545);东乡族和汉族女性CT基因型频率分别为39%和21.9%,分布有统计学差异(x~2=4.272,P=0.039)。
6.东乡族NC组和T2DM组C+CC基因型与T+CT基因型间BMI、腰围、WHR、FPG、FINS、HOMA-IR、血压、血脂差异均无统计学意义(P＞0.05)。
7.汉族T2DM患者C+CC型组HOMA-IR明显高于T+T-F+CT型组,差异有统计学意义(t=2.267,P=0.026)。两组BMI、腰围、TC、TG、HDL-C、LDL-C差异均无统计学意义(P＞0.05)。
8.东乡族和汉族男性、女性各基因型频率及等位基因频率在肥胖组与非肥胖组间无统计学差异(P＞0.05)。
结论:HTR2C基因启动子区-759C/T多态性与T2DM的关系在东乡族和汉族人群中存在差异,该多态性与甘肃东乡族女性T2DM相关联,-759C→T单核苷酸置换可能是抑制T2DM发病的保护性因子。-759C/T多态性与汉族2型糖尿病发生无关。HTR2C基因-759C和-759C/C基因型可能与汉族T2DM患者的胰岛素抵抗有关。HTR2C基因-759C/T多态性可能与东乡族、汉族肥胖发生无关。
Objectives To investigate the association of the -759C/T polymorphism of the 5-HT_(2C) receptor gene(5-hydroxytryptamine 2C receptor,HTR2C) with type 2 diabetes(T2DM) and obesity in Dongxiang and Han population.
Methods The -759C/T polymorphism of the 5-HT_(2C) receptor gene was detected by PCR-ligase detection reaction(PCR-LDR) technique in 100 type 2 diabetics and 126 normal control subjects of Dongxiang population,133 type 2 diabetics and 135 normal control subjects of Han population.At the same time,we measured the body height,body weight, waist circumference,hip circumference,systolic blood pressure(SBP),diastolic blood pressure(DBP).Total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C) and fasting blood glucose levels were determined by automatic biochemistry analyzer.Fasting blood insulin concentration was measured using insulin radioimmunoassay kit.The homeostasis model assessment insulin resistance index(HOMA-IR) was calculated by the formula:fasting glucose(millimoles per liter)×fasting insulin(microunits per milliliter)/22.5.
Results
1.Clinical data comparison between the diabetic group and control group in Dongxiang population:In the diabetic group,the levels of waist circumference,waist-to-hip ratio, fasting blood glucose,fasting blood insulin,HOMA-IR,systolic blood pressure(SBP), diastolic blood pressure(DBP),triglyceride(TG),and low density lipoprotein cholesterol (LDL-C) were significantly higher than those in the control group(P＜0.05).
2.Clinical data comparison between the diabetic group and control group in Han population: In the diabetic group,the levels of waist circumference,waist-to-hip ratio,fasting blood glucose,fasting insulin,HOMA-IR,SBP,and TG were significantly higher than those in the control group(P＜0.05).HDL-C was significantly lower than it in the control group (P＜0.05).
3.In Dongxiang population,the frequency of CC,CT genotypes in female diabetics and normal control subjects were 80.6%,19.4%and 61%,39%,respectively.The frequency of CT genotype was significantly lower in the female diabetics than in the normal control subjects(x~2=3.950,P=0.047),and the allele frequencies showed no statistical difference between two groups(x~2=3.210,P=0.073).The frequency of C and T hemizygote also showed no statistical difference between male diabetics and normal control subjects(x~2= 0.122,P=0.727).
4.In Han population,the frequency of genotypes and alleles of -759C/T showed no statistical difference between diabetics and normal control subjects(P＞0.05).
5.The frequency of C and T allele showed no statistical difference between Dongxiang and Han population in normal control subjects(x~2=3.413,P=0.065).The frequency of C and T hemizygote showed no significantly difference between male Dongxiang and Han population(x~2=0.367,P=0.545).The frequency of CT genotype in female Dongxiang and Han population were 39%and 21.9%,respectively.The distribution of CT genotype showed significantly difference between two populations(x~2= 4.272,P=0.039).
6.In Dongxiang population,the BMI,WC,WHR,FPG,Fins,BP,TC,TG,HDL-C,and LDL-C were no significantly difference between the C+CC genotype and T+CT genotype in control group and type 2 diabetic group respectively(P＞0.05).
7.In Han population,the HOMA-IR was significantly higher in C+CC genotype than in T+CT+TT genotype(t=2.267,P=0.026).
8.The frequency of genotypes and alleles of -759C/T showed no statistical difference between obesity and control subjects in Dongxiang and Han population.
Conclusions Thc correlation between the -759C/T polymorphism of the HTR2C gene and type 2 diabetes may have ethnic difference.In Dongxiang population,the polymorphism was related to the occurrence of T2DM in female.-759C→T may be a protective factor for the development of T2DM.The polymorphism was not related to the occurrence of T2DM in Han population.HTR2C gene -759CC genotype and -759C hemizygote may be associated with the higher HOMA-IR in type 2 diabetic patients of Han population.The -759C/T polymorphism of the HTR2C gene was not associated with obesity in both Dongxiang and Han population.
方法:采用病例对照的研究方法,应用聚合酶链反应(polymerase chain reaction,PCR)-连接酶检测反应(ligase detection reaction,LDR)方法检测东乡族100名2型糖尿病患者(T2DM组)和126名正常对照者(NC组)及汉族133名T2DM患者和135名正常对照者HTR2C基因-759C/T多态性。同时测量身高、体重、腰围、臀围,血压,计算体质量指数(BMI)=体重/身高~2(kg/m~2),腰臀比(WHR)=腰围/臀围。取空腹外周静脉血用全自动生化分析仪测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG),放射免疫法测定空腹胰岛素(FINS)。按稳态模式评估法计算胰岛素抵抗指数(HOMA-IR=FPG×FINS/22.5)。
结果:
1.东乡族T2DM组与NC组临床资料比较:T2DM组腰围、WHR、FPG、FINS、HOMA-IR、收缩压、舒张压、TG、LDL-C均高于NC组,差别有统计学意义(P＜0.05)。
2.汉族T2DM组与NC组临床资料比较:T2DM组腰围、WHR、FPG、FINS、HOMA-IR、收缩压、TG均高于NC组(P＜0.05),T2DM组HDL-C低于NC组,差别有统计学意义(P＜0.05)。
3.东乡族女性NC组和T2DM组CC、CT基因型频率分别为61%、39%和80.6%、19.4%,T2DM组CT基因型频率明显低于NC组(x~2=3.950,P=0.047,OR=0.378,95%CI0.145-0.987);两组C、T等位基因频率分布无统计学差异(x~2=3.210,P=0.073)。男性NC组和T2DM组C、T半合子型频率分布无统计学差异(x~2=0.122,P=0.727)。
4.汉族NC组与T2DM组间男性、女性各基因型频率及等位基因频率分布无统计学差异(P＞0.05)。
5.在正常对照人群,东乡族和汉族C、T等位基因频率分布差异无统计学意义(x~2=3.413,P=0.065)。两民族男性半合子型频率分布差异无统计学意义(x~2=0.367,P=0.545);东乡族和汉族女性CT基因型频率分别为39%和21.9%,分布有统计学差异(x~2=4.272,P=0.039)。
6.东乡族NC组和T2DM组C+CC基因型与T+CT基因型间BMI、腰围、WHR、FPG、FINS、HOMA-IR、血压、血脂差异均无统计学意义(P＞0.05)。
7.汉族T2DM患者C+CC型组HOMA-IR明显高于T+T-F+CT型组,差异有统计学意义(t=2.267,P=0.026)。两组BMI、腰围、TC、TG、HDL-C、LDL-C差异均无统计学意义(P＞0.05)。
8.东乡族和汉族男性、女性各基因型频率及等位基因频率在肥胖组与非肥胖组间无统计学差异(P＞0.05)。
结论:HTR2C基因启动子区-759C/T多态性与T2DM的关系在东乡族和汉族人群中存在差异,该多态性与甘肃东乡族女性T2DM相关联,-759C→T单核苷酸置换可能是抑制T2DM发病的保护性因子。-759C/T多态性与汉族2型糖尿病发生无关。HTR2C基因-759C和-759C/C基因型可能与汉族T2DM患者的胰岛素抵抗有关。HTR2C基因-759C/T多态性可能与东乡族、汉族肥胖发生无关。
Objectives To investigate the association of the -759C/T polymorphism of the 5-HT_(2C) receptor gene(5-hydroxytryptamine 2C receptor,HTR2C) with type 2 diabetes(T2DM) and obesity in Dongxiang and Han population.
Methods The -759C/T polymorphism of the 5-HT_(2C) receptor gene was detected by PCR-ligase detection reaction(PCR-LDR) technique in 100 type 2 diabetics and 126 normal control subjects of Dongxiang population,133 type 2 diabetics and 135 normal control subjects of Han population.At the same time,we measured the body height,body weight, waist circumference,hip circumference,systolic blood pressure(SBP),diastolic blood pressure(DBP).Total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C) and fasting blood glucose levels were determined by automatic biochemistry analyzer.Fasting blood insulin concentration was measured using insulin radioimmunoassay kit.The homeostasis model assessment insulin resistance index(HOMA-IR) was calculated by the formula:fasting glucose(millimoles per liter)×fasting insulin(microunits per milliliter)/22.5.
Results
1.Clinical data comparison between the diabetic group and control group in Dongxiang population:In the diabetic group,the levels of waist circumference,waist-to-hip ratio, fasting blood glucose,fasting blood insulin,HOMA-IR,systolic blood pressure(SBP), diastolic blood pressure(DBP),triglyceride(TG),and low density lipoprotein cholesterol (LDL-C) were significantly higher than those in the control group(P＜0.05).
2.Clinical data comparison between the diabetic group and control group in Han population: In the diabetic group,the levels of waist circumference,waist-to-hip ratio,fasting blood glucose,fasting insulin,HOMA-IR,SBP,and TG were significantly higher than those in the control group(P＜0.05).HDL-C was significantly lower than it in the control group (P＜0.05).
3.In Dongxiang population,the frequency of CC,CT genotypes in female diabetics and normal control subjects were 80.6%,19.4%and 61%,39%,respectively.The frequency of CT genotype was significantly lower in the female diabetics than in the normal control subjects(x~2=3.950,P=0.047),and the allele frequencies showed no statistical difference between two groups(x~2=3.210,P=0.073).The frequency of C and T hemizygote also showed no statistical difference between male diabetics and normal control subjects(x~2= 0.122,P=0.727).
4.In Han population,the frequency of genotypes and alleles of -759C/T showed no statistical difference between diabetics and normal control subjects(P＞0.05).
5.The frequency of C and T allele showed no statistical difference between Dongxiang and Han population in normal control subjects(x~2=3.413,P=0.065).The frequency of C and T hemizygote showed no significantly difference between male Dongxiang and Han population(x~2=0.367,P=0.545).The frequency of CT genotype in female Dongxiang and Han population were 39%and 21.9%,respectively.The distribution of CT genotype showed significantly difference between two populations(x~2= 4.272,P=0.039).
6.In Dongxiang population,the BMI,WC,WHR,FPG,Fins,BP,TC,TG,HDL-C,and LDL-C were no significantly difference between the C+CC genotype and T+CT genotype in control group and type 2 diabetic group respectively(P＞0.05).
7.In Han population,the HOMA-IR was significantly higher in C+CC genotype than in T+CT+TT genotype(t=2.267,P=0.026).
8.The frequency of genotypes and alleles of -759C/T showed no statistical difference between obesity and control subjects in Dongxiang and Han population.
Conclusions Thc correlation between the -759C/T polymorphism of the HTR2C gene and type 2 diabetes may have ethnic difference.In Dongxiang population,the polymorphism was related to the occurrence of T2DM in female.-759C→T may be a protective factor for the development of T2DM.The polymorphism was not related to the occurrence of T2DM in Han population.HTR2C gene -759CC genotype and -759C hemizygote may be associated with the higher HOMA-IR in type 2 diabetic patients of Han population.The -759C/T polymorphism of the HTR2C gene was not associated with obesity in both Dongxiang and Han population.
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