Association of 4p14 and 6q27 variation with Graves disease: a case-control study and a meta-analysis of available evidence.
Association of 4p14 and 6q27 variation with Graves disease: a case-control study and a meta-analysis of available evidence.
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4p14 和 6q27 变异与格雷夫斯病的关联：病例对照研究和现有证据的荟萃分析
DOI：
10.1186/s12881-017-0406-7
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发表时间：
2017-05-18
影响因子：
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通讯作者：
Song ZJ
中科院分区：
文献类型：
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作者：
Li FM;Liu L;Pang LN;Shen M;Lu HW;Zhang XH;Chu X;Song ZJ
Graves病(GD)的病因在很大程度上尚不清楚。然而，遗传因素被认为起着主要作用。最近在中国汉族人样本收集中的一项全基因组关联研究发现，在染色体4p14和6q27带上有两个新的Graves病(GD)风险基因座。在这项研究中，我们旨在调查这些与山东潍坊汉族人群的关联，并对其与GD的关联进行Meta分析。采用病例对照研究方法，探讨山东潍坊地区汉族人群中4p14和6q27基因变异与GD易感性的关系。选择位于染色体4p14的SNP rs6832151和位于染色体6q27的SNP rs9355610对2,382例GD患者和3,092例无血缘关系的正常人进行基因分型。在ABI7900平台上采用TaqMan实时定量聚合酶链式反应技术进行SNP基因分型。对当前样本集中的数据和以前研究中获得的数据进行了荟萃分析。关联分析显示，位于4p14的rs6832151(优势比 = 1.27，P等位基因 = 1.48 × 10−9)和位于6q27的rs9355610(OR = 1.10，P等位基因 = 1.04 × 10−2)均与GD易感性相关。通过遗传模型分析发现，rs6832151应采用隐性遗传模式(P隐性 = 2.75 × 10−11)。Rs9355610以显性模式(P显性 = 7.15 × 10−3)为主，隐性模式分析无显著关联(P隐性 = 0.13)。Meta分析从本样本获得的10,781例病例和16,304名对照的数据以及从先前研究获得的数据证实，使用固定模型(OR = 1.27，95%CI：1.22~1.32；I2 = 0%)，4p14位点的rs6832151与GD易感性有关。通过对11,306例病例和12,756例对照的Meta分析，采用固定模型(OR = 1.18，95%CI：1.13~1.22；I2 = 41.2%)证实了6q27位点rs9355610与GD易感性的关联。结果表明，山东潍坊汉族人群中，染色体4p14和6q27突变与Graves病相关。
The etiology of the Graves’ disease (GD) is largely unknown. However, genetic factors are believed to play a major role. A recent genome-wide association study in a Han Chinese sample collection revealed two new Graves’ disease (GD) risk loci within chromosome band 4p14 and 6q27. In this study, we aimed to investigate these associations with Weifang Han Chinese population of Shandong province and perform a meta-analysis of associations with GD. A case–control study was conducted to investigate association of variation within 4p14 and 6q27 to GD susceptibility in Weifang Han Chinese population of Shandong province. SNP rs6832151 at chromosome 4p14 and SNP rs9355610 at chromosome 6q27 was selected for genotyping in 2,382 GD patients and 3,092 unrelated controls. SNP genotyping was performed using TaqMan Real-time PCR technique assays on ABI7900 platform. A meta-analysis was performed with the data obtained in the current sample-set and those available from prior studies. Association analysis revealed both rs6832151 located in 4p14 (odds ratio (OR) = 1.27, P Allelic = 1.48 × 10−9) and rs9355610 located in 6q27 (OR = 1.10, P Allelic = 1.04 × 10−2) was associated with GD susceptibility. By model of inheritance analysis, we found the recessive model should be preferred (P Recessive = 2.75 × 10−11) for rs6832151. The dominant model should be preferred (P Dominant = 7.15 × 10−3) for rs9355610, whereas analysis of recessive model showed no significant association (P Recessive = 0.13). Meta-analysis with the data of 10,781 cases and 16,304 controls obtained from present sample-set and those available from prior studies confirmed association of rs6832151 at 4p14 with GD susceptibility using a fixed model (OR = 1.27, 95% CI: 1.22 to 1.32; I2 = 0%). Meta-analysis with the data of 11,306 cases and 12,756 controls confirmed association of rs9355610 at 6q27 with GD susceptibility using a fixed model (OR = 1.18, 95% CI: 1.13 to 1.22; I2 = 41.2%). Our findings showed that chromosome 4p14 and 6q27 variants were associated with Graves’ disease in Weifang Han Chinese population of Shandong province.