花生四烯酸5-脂氧合酶激活蛋白-1340 T/G单核甘酸多态性与急性心肌梗死相关性研究
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摘要
目的探讨花生四烯酸5-脂氧合酶激活蛋白(ALOX5AP)-1340 T/G单核甘酸多态性与急性心肌梗死相关性。方法选取自2015年2月至2017年6月于北部战区总医院心血管内科就诊的326例急性心肌梗死患者为急性心肌梗死组,另选取同期326例因胸痛住院并经冠状动脉造影检查显示为阴性的患者为阴性组。采用经典的测序分析ALOX5AP-1340 T/G单核甘酸多态位点基因型和等位基因频率的分布情况。采用多元Logistic回归分析法分析急性心肌梗死发病的独立危险因素。结果 ALOX5AP-1340 T/G单核苷酸多态位点存在TT型、TG型和GG型3种基因型。阴性组ALOX5AP-1340 T/G单核苷酸位点的三种基因型TT型、TG型和GG型的分布频率为29.1%(95/326)、49.1%(160/326)、21.8%(71/326),急性心肌梗死组的分布频率为24.5%(80/326)、44.5%(145/326)、31.0%(101/326);ALOX5AP-1340 T/G单核苷酸多态位点T和G等位基因分布频率在急性心肌梗死患者为46.7%(305/652)、53.3%(347/652),在阴性组的分布频率为53.7%(350/652)、46.3%(302/652)。两组患者ALOX5AP基因-1340 T/G单核苷酸多态位点分布比较,差异有统计学意义(P<0.05;OR=1.32;95%可信区间1.06～1.64)。多元回归分析结果显示,ALOX5AP-1340 T/G单核苷酸多态G等位基因是急性心肌梗死发病的独立危险因素(P<0.05)。结论 ALOX5AP-1340 T/G等位基因可能是急性心肌梗死发病的危险因素,在冠状动脉粥样硬化不稳定斑块形成过程中起重要作用。
Objective To investigate the association between the arachidonate 5-lipoxygenase acttvating protein(ALOX5 AP)-1340 T/G variant and acute myocardial infarction(AMI).Methods A retrospective study was performed on 326 cases of patients with AMI who were admitted form February 2015 to June 2017.The 326 cases of AMI patients were divided into the AMI group,during the same period,the other 326 cases of patients with chest pain and got negative result of coronary angiography were divided into the control group.Classic sequencing was used to analyze the genotype and allele frequency distribution of ALOX5 AP-1340 T/G mononucleotide polymorphism locus.Results There were TT,TG and GG genotypes in the single nucleotide polymorphisms of ALOX5 AP-1340 T/G.In the control group,the distribution frequency of TT,TG and GG genotypes of ALOX5 AP-1340 T/G single nucleotide loci was 29.1%(95/326),49.1%(160/326),21.8%(71/326),and that of the AMI group was 24.5%(80/326),44.5%(145/326) and 31.0%(101/326).ALOX5 AP-1340 T/G single nucleotide polymorphism site T and G allele distribution frequency in patients with AMI was 46.7%(305/652) and 53.3%(347/652),53.7%(355/652) and 46.3%(302/652) in the control group.The distribution of ALOX5 AP-1340 T/G SNPS in the two groups was compared,and the difference was statistically significant(P<0.05;OR=1.32;95%CI 1.06-1.64).Multiple regression analysis showed that ALOX5 AP-1340 T/G single nucleotide polymorphic G allele was an independent risk factor of AMI(P<0.05).Conclusion ALOX5 AP-1340 T/G allele may be a risk factor of acute myocardial infarction,and ALOX5 AP-1340 T/G allele plays an important role in the formation of coronary atherosclerotic unstable plaques.
Objective To investigate the association between the arachidonate 5-lipoxygenase acttvating protein(ALOX5 AP)-1340 T/G variant and acute myocardial infarction(AMI).Methods A retrospective study was performed on 326 cases of patients with AMI who were admitted form February 2015 to June 2017.The 326 cases of AMI patients were divided into the AMI group,during the same period,the other 326 cases of patients with chest pain and got negative result of coronary angiography were divided into the control group.Classic sequencing was used to analyze the genotype and allele frequency distribution of ALOX5 AP-1340 T/G mononucleotide polymorphism locus.Results There were TT,TG and GG genotypes in the single nucleotide polymorphisms of ALOX5 AP-1340 T/G.In the control group,the distribution frequency of TT,TG and GG genotypes of ALOX5 AP-1340 T/G single nucleotide loci was 29.1%(95/326),49.1%(160/326),21.8%(71/326),and that of the AMI group was 24.5%(80/326),44.5%(145/326) and 31.0%(101/326).ALOX5 AP-1340 T/G single nucleotide polymorphism site T and G allele distribution frequency in patients with AMI was 46.7%(305/652) and 53.3%(347/652),53.7%(355/652) and 46.3%(302/652) in the control group.The distribution of ALOX5 AP-1340 T/G SNPS in the two groups was compared,and the difference was statistically significant(P<0.05;OR=1.32;95%CI 1.06-1.64).Multiple regression analysis showed that ALOX5 AP-1340 T/G single nucleotide polymorphic G allele was an independent risk factor of AMI(P<0.05).Conclusion ALOX5 AP-1340 T/G allele may be a risk factor of acute myocardial infarction,and ALOX5 AP-1340 T/G allele plays an important role in the formation of coronary atherosclerotic unstable plaques.
引文
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[7] 李志栋,张效林,韩雅玲,等.ALOX5AP基因T(-1340)G多态性与中国北方汉族人群冠状动脉粥样硬化性心脏病发病的关联[J].中国组织工程研究与临床康复,2009,13(50):9974-9978.
[8] He G,Ye S,Hui J,et al.Interrelationships between ALOX5AP polymorphisms,serum leukotriene B4 level and risk of acute coronary syndrome[J].PLoS One,2014,9(9):e106596.
[9] Yang D,Huang X,Cui C,et al.Genetic Variants in the transcriptional regulatory region of the ALOX5AP gene and susceptibility to ischemic stroke in Chinese populations[J].Scientific Reports,2016,6(1):29513.
[10] Zhang SY,Xu ML,Zhang CE,et al.Association of ALOX5AP gene single nucleotide polymorphisms and cerebral infarction in the Han population of northern China[J].BMC Med Genet,2012,13:61.
[11] Shah SH,Hauser ER,Crosslin D,et al.ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention[J].Atherosclerosis,2008,201(1):148-154.
[12] 解晓蕊,李晓莉,杨朴,等.尼可地尔联合阿托伐他汀对冠状动脉慢血流患者炎症反应、血管内皮功能的影响及安全性分析[J].现代生物医学进展,2017,17(34):6705-6708.
[13] Alwan A,Youhanna SC,Platt DE,et al.ALOX5AP gene variants show differential association with coronary artery disease in different populations[J].J Community Genet,2010,1(3):107-115.
[14] Gammelmark A,Nielsen MS,Lundbye-Christensen S,et al.Common polymorphisms in the 5-lipoxygenase pathway and risk of incident myocardial infarction:a danish case-cohort study[J].PLoS One,2016,11(11):e0167217.
[15] Schentrup AM,Allayee H,Lima JJ,et al.Genotyping the GGGCGG tandem repeat promoter polymorphism in the 5-lipoxygenase enzyme gene (ALOX5) by pyrosequencing assay[J].Genet Test Mol Biomarkers,2009,13(3):361-365.
[2] 周广怡.5-脂氧合酶炎性途径对动脉粥样硬化的调控机制研究[D].南京大学,2010:1-90.
[3] Libby P,Okamoto Y,Rocha VZ,et al.Inflammation in atherosclerosis:transition from theory to practice[J].Circ J,2010,74(2):213-220.
[4] 蔡丽娟,杨美雯,洪芬芳,等.白三烯与动脉粥样硬化关系的研究新进展[J].南昌大学学报(医学版),2016,56(6):80-84.
[5] 邢冬梅,杨兴隆,李佩云,等.5-脂氧合酶、同型半胱氨酸与颈动脉粥样硬化稳定性的关系研究[J].重庆医学,2017,46(34):4783-4786.
[6] Fan Y,Chen H,Li A,et al.A promoter polymorphism (rs17222919,-1316T/G) of ALOX5AP gene is associated with decreased risk of ischemic stroke in two independent Chinese populations[J].PLoS One,2015,10(3):e0122393.
[7] 李志栋,张效林,韩雅玲,等.ALOX5AP基因T(-1340)G多态性与中国北方汉族人群冠状动脉粥样硬化性心脏病发病的关联[J].中国组织工程研究与临床康复,2009,13(50):9974-9978.
[8] He G,Ye S,Hui J,et al.Interrelationships between ALOX5AP polymorphisms,serum leukotriene B4 level and risk of acute coronary syndrome[J].PLoS One,2014,9(9):e106596.
[9] Yang D,Huang X,Cui C,et al.Genetic Variants in the transcriptional regulatory region of the ALOX5AP gene and susceptibility to ischemic stroke in Chinese populations[J].Scientific Reports,2016,6(1):29513.
[10] Zhang SY,Xu ML,Zhang CE,et al.Association of ALOX5AP gene single nucleotide polymorphisms and cerebral infarction in the Han population of northern China[J].BMC Med Genet,2012,13:61.
[11] Shah SH,Hauser ER,Crosslin D,et al.ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention[J].Atherosclerosis,2008,201(1):148-154.
[12] 解晓蕊,李晓莉,杨朴,等.尼可地尔联合阿托伐他汀对冠状动脉慢血流患者炎症反应、血管内皮功能的影响及安全性分析[J].现代生物医学进展,2017,17(34):6705-6708.
[13] Alwan A,Youhanna SC,Platt DE,et al.ALOX5AP gene variants show differential association with coronary artery disease in different populations[J].J Community Genet,2010,1(3):107-115.
[14] Gammelmark A,Nielsen MS,Lundbye-Christensen S,et al.Common polymorphisms in the 5-lipoxygenase pathway and risk of incident myocardial infarction:a danish case-cohort study[J].PLoS One,2016,11(11):e0167217.
[15] Schentrup AM,Allayee H,Lima JJ,et al.Genotyping the GGGCGG tandem repeat promoter polymorphism in the 5-lipoxygenase enzyme gene (ALOX5) by pyrosequencing assay[J].Genet Test Mol Biomarkers,2009,13(3):361-365.