GUCY1A3基因位点rs7692387单核苷酸多态性与冠状动脉粥样硬化性心脏病的相关性研究
|
摘要
目的探讨GUCY1A3基因位点rs7692387单核苷酸多态性与冠状动脉粥样硬化性心脏病(冠心病)的相关性。方法选取延边大学附属医院收集延边地区汉族冠心病患者204例(冠心病组)以及健康体检的正常人群201例(对照组)。采用基于荧光标记单碱基延伸原理的SNa Pshot技术对GUCY1A3基因位点rs7692387单核苷酸多态性进行分型检测。结果冠心病组和对照组的GUCY1A3基因位点rs7692387的基因型分布均符合Hardy-Weinberg平衡定律。冠心病组GG基因型频率高于对照组,而对照组GA+AA基因型频率高于冠心病组,差异有统计学意义(P<0.05)。G和A两等位基因频率分布差异亦有统计学意义(P<0.05)。应用Logistic回归分析调整混杂因素,差异有统计学意义(P<0.05),并发现GUCY1A3基因位点rs7692387的GG基因型可增加冠心病的患病风险(O^^R=1.543,95%CI:1.022,2.327,P=0.039),而A等位基因可降低冠心病的患病风险(O^^R=0.691,95%CI:0.494,0.968,P=0.031)。结论延边地区汉族人群GUCY1A3基因位点rs7692387单核苷酸多态性可能与冠心病具有相关性,其GG基因型很可能是冠心病发病的易感基因型,而A等位基因可能是冠心病的保护性基因。
Objective To investigate the correlation between single nucleotide polymorphisms at rs7692387 site of GUCY1 A3 gene and coronary atherosclerotic heart disease(CAD). Methods Totally 204 patients with CAD(CAD group) and 201 healthy volunteers(control group) from Yanbian Han population of Yanbian University Hospital were involved in this study. SNa Pshot technique was utilized to identify single nucleotide polymorphisms at rs7692387 site of GUCY1 A3 gene. Statistical analysis was performed for the association between polymorphisms and CAD. Results The genotype frequency at rs7692387 site of GUCY1 A3 gene in both groups fitted the HardyWeinberg equilibriumin. Frequency of GG genotype in the CAD group was significantly higher than that in the control group(P < 0.05), while frequency of GA + AA genotype in the control group was dramatically higher than that in CAD group(P < 0.05). G and A allele were differently distributed in two groups(P < 0.05). GG genotype at rs7692387 site of GUCY1 A3 gene increased risk of CAD(O^^R = 543, 95% CI = 1.022, 2.327, P = 0.039) while the A allele could reduce the risk of CAD(O^^R = 0.691, 95% CI = 0.494, 0.968, P = 0.031). Logistic regression analysis plus adjustments for the confounding factors confirmed these results. Conclusion Single nucleotide polymorphisms at rs7692387 site of GUCY1 A3 gene is associated with CAD in Yanbian Han population, and GG genotype is potentially detrimental while A allele may be beneficial for occurrence of CAD.
Objective To investigate the correlation between single nucleotide polymorphisms at rs7692387 site of GUCY1 A3 gene and coronary atherosclerotic heart disease(CAD). Methods Totally 204 patients with CAD(CAD group) and 201 healthy volunteers(control group) from Yanbian Han population of Yanbian University Hospital were involved in this study. SNa Pshot technique was utilized to identify single nucleotide polymorphisms at rs7692387 site of GUCY1 A3 gene. Statistical analysis was performed for the association between polymorphisms and CAD. Results The genotype frequency at rs7692387 site of GUCY1 A3 gene in both groups fitted the HardyWeinberg equilibriumin. Frequency of GG genotype in the CAD group was significantly higher than that in the control group(P < 0.05), while frequency of GA + AA genotype in the control group was dramatically higher than that in CAD group(P < 0.05). G and A allele were differently distributed in two groups(P < 0.05). GG genotype at rs7692387 site of GUCY1 A3 gene increased risk of CAD(O^^R = 543, 95% CI = 1.022, 2.327, P = 0.039) while the A allele could reduce the risk of CAD(O^^R = 0.691, 95% CI = 0.494, 0.968, P = 0.031). Logistic regression analysis plus adjustments for the confounding factors confirmed these results. Conclusion Single nucleotide polymorphisms at rs7692387 site of GUCY1 A3 gene is associated with CAD in Yanbian Han population, and GG genotype is potentially detrimental while A allele may be beneficial for occurrence of CAD.
引文
[1]LYU Y,JIANG X,DAI W.The roles of a novel inflammatory neopterin in subjects with coronary atherosclerotic heart disease[J].Int Immunopharmacol,2015,24(2):169-172.
[2]HOLFMANN M M,RENNER W.Insight from genomewide association studies into coronary heart disease[J].Pharmacogenomics,2012,13(4):361-363.
[3]OZAKI K,OHNISHI Y,IIDA A,et al.Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction[J].Nat Genet,2002,32(4):650-654.
[4]JANA WOBST,SIMON VON AMELN,BERNHARD WOLF,et al.Stimulators of the soluble guanylyl cyclase:promising functional insights from rare coding atherosclerosis-related GUCY1A3 variants[J].Basic Res Cardiol,2016,111(4):51.
[5]TAKIMOTO E.Cyclic GMP-dependent signaling in cardiac myocytes[J].Circ J,2012,76(8):1819-1825.
[6]CHEN W W,GAO R L,LIU L S,et al.The general views of report of Chinese cardiovascular disease 2014[J].Chin Circ J,2015,30(7):617-622.
[7]单雪峰,刘成,孙清超,等.新疆维吾尔族PCSK9基因多态性与冠心病的相关性探讨[J].中西医结合心脑血管病杂志,2016,14(17):1953-1958.
[8]高静,刘相飞,陈玉东.黄三角地区人群中PDGF-D基因多态性与冠心病的相关性[J].中国动脉硬化杂志,2016,24(9):944-948.
[9]DANDONA S,ROBERTS R.The role of genetic risk factors in coronary artery disease[J].Curr Cardiol Rep,2014,16(5):479.
[10]LU X,WANG L,CHEN S,et al.Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease[J].Nat Genet,2012,44(8):890-894.
[11]雷铁涛.可溶性鸟苷酸环化酶α1和β1亚基在雄性大鼠生殖系统中表达的研究[D].南京:南京农业大学,2006.
[12]石蕊,李玉明.可溶性鸟苷酸环化酶基因突变与盐敏感性高血压[J].武警医学院学报,2002,11(1):62-63.
[13]FRIEBE A,KOESLING D.The function of NO-sensitive guanylyl cyclase:what we can learn from genetic mouse models[J].Nitric Oxide,2009,21(3):149-156.
[14]SCHMIDT H H,HOFMANN F,STASCH J P.c GMP:Generators,effectors and therapeutic implications[M].Germany:Springer,2009:485-488.
[15]IRVINE J C,GANTHAVEE V,LOVE J E,et al.The soluble guanylyl cyclase activator Bay 58-2667 selectively limits cardiomyocyte hypertrophy[J].PLo S One,2012,7(11):e44481.
[2]HOLFMANN M M,RENNER W.Insight from genomewide association studies into coronary heart disease[J].Pharmacogenomics,2012,13(4):361-363.
[3]OZAKI K,OHNISHI Y,IIDA A,et al.Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction[J].Nat Genet,2002,32(4):650-654.
[4]JANA WOBST,SIMON VON AMELN,BERNHARD WOLF,et al.Stimulators of the soluble guanylyl cyclase:promising functional insights from rare coding atherosclerosis-related GUCY1A3 variants[J].Basic Res Cardiol,2016,111(4):51.
[5]TAKIMOTO E.Cyclic GMP-dependent signaling in cardiac myocytes[J].Circ J,2012,76(8):1819-1825.
[6]CHEN W W,GAO R L,LIU L S,et al.The general views of report of Chinese cardiovascular disease 2014[J].Chin Circ J,2015,30(7):617-622.
[7]单雪峰,刘成,孙清超,等.新疆维吾尔族PCSK9基因多态性与冠心病的相关性探讨[J].中西医结合心脑血管病杂志,2016,14(17):1953-1958.
[8]高静,刘相飞,陈玉东.黄三角地区人群中PDGF-D基因多态性与冠心病的相关性[J].中国动脉硬化杂志,2016,24(9):944-948.
[9]DANDONA S,ROBERTS R.The role of genetic risk factors in coronary artery disease[J].Curr Cardiol Rep,2014,16(5):479.
[10]LU X,WANG L,CHEN S,et al.Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease[J].Nat Genet,2012,44(8):890-894.
[11]雷铁涛.可溶性鸟苷酸环化酶α1和β1亚基在雄性大鼠生殖系统中表达的研究[D].南京:南京农业大学,2006.
[12]石蕊,李玉明.可溶性鸟苷酸环化酶基因突变与盐敏感性高血压[J].武警医学院学报,2002,11(1):62-63.
[13]FRIEBE A,KOESLING D.The function of NO-sensitive guanylyl cyclase:what we can learn from genetic mouse models[J].Nitric Oxide,2009,21(3):149-156.
[14]SCHMIDT H H,HOFMANN F,STASCH J P.c GMP:Generators,effectors and therapeutic implications[M].Germany:Springer,2009:485-488.
[15]IRVINE J C,GANTHAVEE V,LOVE J E,et al.The soluble guanylyl cyclase activator Bay 58-2667 selectively limits cardiomyocyte hypertrophy[J].PLo S One,2012,7(11):e44481.