七个全基因组关联分析提示的易感位点与汉族人群年龄相关性黄斑变性的相关性分析

Association analysis of seven single nucleotide polymorphisms identified by genome-wide association study with age-related macular degeneration among ethnic Han Chinese population

目的验证全基因组关联分析所发现的7个单核苷酸多态性(single nucleotide polymorphisms,SNPs),包括rs13278062(TNFRSF10A)、rs3750846(ARMS2-HTRA1)、rs429358(APOE)、rs5817082(CEPT)、rs2043085(LIPC)、rs1626340(TGFBR1)以及rs8135665(SLC16A8)与四川汉族人群年龄相关性黄斑变性(age-related macular degeneration,AMD)的相关性。方法采用病例-对照研究,用飞行质谱对576例湿性AMD患者和572例健康对照进行SNPs分型并通过Sanger测序进行验证。在两组各SNP位点基因型分布均满足Hardy-Weinberg平衡的前提下,分析各位点的遗传模式,并比较其等位基因与基因型频率的分布。结果TNFRSF10A rs13278062在杂合子模型(P=0.000,OR=1.529,95%CI=1.196-1.954)和显性模型(P=0.002,OR=1.459,95%CI=1.154-1.865)下在两组之间存在显著的差异。结论TNFRSF10A rs13278062在杂合或显性模式下与AMD相关,携带rs13278062GT和rs13278062TT+GT的个体更容易患AMD。

Objective To assess the association of 7 single nucleotide polymorphisms(SNPs)including rs13278062(TNFRSF10A),rs3750846(ARMS2-HTRA1),rs429358(APOE),rs5817082(CEPT),rs2043085(LIPC),rs1626340(TGFBR1),and rs8135665(SLC16A8)identified through genome-wide association study(GWAS)with age-related macular degeneration(AMD)among ethnic Han Chinese from Sichuan,China.Methods A cohort of 576 AMD patients and 572 healthy controls were enrolled in a case-control study.The SNPs were genotyped by a Mass array MALDI-TOF System.On the premise that the genotype distribution of each SNP locus in both groups satisfied Hardy-Weinberg equilibrium,the genetic pattern was analyzed and the scores of allele and genotype frequencies ware compared.Results There was a significant association between TNFRSF10A rs13278062 and AMD under the heterozygous model(P=0.000,OR=1.529,95%CI=1.196-1.954)and the dominant model(P=0.002,OR=1.459,95%CI=1.154-1.865),suggesting that subjects carrying rs13278062GT and rs13278062TT+GT are more likely to develop the AMD,whereas no significant difference was observed for rs13278062 under other models.No association was detected with the other six SNPs and AMD under various genetic models.Conclusion This case-control association study has indicated that TNFRSF10A rs13278062 is associated with AMD under the heterozygous and dominant models,suggesting that the TNFRSF10A variant may be involved in the development of AMD among ethnic Han Chinese population.