Association Analysis of Single Nucleotide Polymorphisms in C1QTNF6, RAC2, and an Intergenic Region at 14q32.2 with Graves' Disease in Chinese Han Population
Association Analysis of Single Nucleotide Polymorphisms in C1QTNF6, RAC2, and an Intergenic Region at 14q32.2 with Graves' Disease in Chinese Han Population
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C1QTNF6、RAC2及14q32.2基因间区域单核苷酸多态性与中国汉族格雷夫斯病的关联分析
DOI：
10.1089/gtmb.2017.0009
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发表时间：
2017
影响因子：
1.4
通讯作者：
Huang Wei
中科院分区：
文献类型：
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作者：
Zhang Xiao-Hong;Shen Min;Liu Lin;Li Fa-Mei;Hu Peng-Chen;Hua Qi;Zhang Jing;Pang Li-Nan;Lu Hong-Wen;Wang Zhi-Min;Chu Xun;Huang Wei
背景：在最近的一项研究中，发现1qtnf6基因22q12.3、therac2基因22q13.1和14q32.2基因间区域的变异与Graves病（GD）的风险相关。我们的目的是在汉族人群的独立样本集中验证这些与GD的关联。方法：我们通过对这三个区域中最显著相关的单核苷酸多态性（snp）进行基因分型来研究这些关联。选择位于基因间区14q32.2的Rs1456988、位于inc1qtnf6at 22q12.3的rs229527和位于rac2at 22q13.1的rs2284038进行基因分型。通过一项病例对照研究对这三个snp进行基因分型，该研究包括2382名GD患者和3092名来自北方汉族血统的无关健康对照。在ABI7900平台上使用TaqMan检测进行基因分型。结果：我们发现rs229527等位基因与inc1qtnf6（优势比[OR] = 1.23，可信区间[95% CI]: 1.12-1.33,pAllelic= 4.60 × 10−6）和rs2284038等位基因与rac2 （OR = 1.10, 95% CI: 1.01-0.19,pAllelic= 3.00 × 10−2）均与GD易感性显著相关。然而，位于14q32.2位点的rs1456988 （OR = 1.08, 95% CI: 0.99-1.16,pAllelic= 7.01 × 10−2）无相关性。遗传模型分析表明，显性和隐性模型均与rs229527有显著相关性（OR = 1.24, 95% CI: 1.13 ~ 1.38,pDominant= 9.90 × 10−5;OR = 1.49, 95% CI: 1.19 ~ 1.86, precative = 3.90 × 10−4），显性模型优先。对于rs2284038，隐性模型更受青睐（OR = 1.18, 95% CI: 1.00-1.40, precsive = 4.76 × 10−2），而显性模型分析显示无相关性（OR = 1.10, 95% CI: 0.98-1.22,pDominant= 0.10）。结论：我们的研究结果证实，染色体22q12.3和22q13.1变异与中国汉族独立人群的GD相关；然而，14q32.2与GD没有关联。
Background:Variation within theC1QTNF6gene at 22q12.3, theRAC2gene at 22q13.1, and an intergenic region at 14q32.2 were found to be associated with risk to Graves' disease (GD) in a recent study. We aimed to validate these associations with GD in an independent sample set of Han Chinese population.Methods:We investigated these associations by genotyping the most significantly associated single nucleotide polymorphisms (SNPs) located in these three regions. Rs1456988 within the intergenic region at 14q32.2, rs229527 withinC1QTNF6at 22q12.3, and rs2284038 withinRAC2at 22q13.1 were selected for genotyping. These three SNPs were genotyped using a case–control study that included 2382 GD patients and 3092 unrelated healthy controls from Northern Han Chinese ancestry. The genotyping was performed using TaqMan assays on the ABI7900 platform.Results:We found both the rs229527 allele withinC1QTNF6(odds ratio [OR] = 1.23, confidence interval [95% CI]: 1.12–1.33,pAllelic= 4.60 × 10−6) and the rs2284038 allele withinRAC2(OR = 1.10, 95% CI: 1.01–0.19,pAllelic= 3.00 × 10−2) showed significant associations with GD susceptibility. However, rs1456988 located in 14q32.2 (OR = 1.08, 95% CI: 0.99–1.16,pAllelic= 7.01 × 10−2) showed no association. Analysis of models of inheritance suggested that both the dominant and recessive models showed significant associations for rs229527 (OR = 1.24, 95% CI: 1.13–1.38,pDominant= 9.90 × 10−5; OR = 1.49, 95% CI: 1.19–1.86,pRecessive= 3.90 × 10−4), with the dominant model being preferred. For rs2284038, the recessive model was preferred (OR = 1.18, 95% CI: 1.00–1.40,pRecessive= 4.76 × 10−2), whereas analysis of dominant model showed no association (OR = 1.10, 95% CI: 0.98–1.22,pDominant= 0.10).Conclusions:Our findings confirmed that chromosome 22q12.3 and 22q13.1 variants are associated with GD in an independent Han Chinese population; however, 14q32.2 showed no association with GD.