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
1 Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China .
2 Shanghai-Ministry of Science and Technology (MOST) Key Laboratory of Health and Disease Genomics, Department of Genetics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI) , Shanghai, China .
Genet Test Mol Biomarkers. 2017 Aug;21(8):479-484. doi: 10.1089/gtmb.2017.0009. Epub 2017 Jun 30.
Variation within the C1QTNF6 gene at 22q12.3, the RAC2 gene 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.
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 within C1QTNF6 at 22q12.3, and rs2284038 within RAC2 at 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.
We found both the rs229527 allele within C1QTNF6 (odds ratio [OR] = 1.23, confidence interval [95% CI]: 1.12-1.33, p = 4.60 × 10) and the rs2284038 allele within RAC2 (OR = 1.10, 95% CI: 1.01-0.19, p = 3.00 × 10) showed significant associations with GD susceptibility. However, rs1456988 located in 14q32.2 (OR = 1.08, 95% CI: 0.99-1.16, p = 7.01 × 10) 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, p = 9.90 × 10; OR = 1.49, 95% CI: 1.19-1.86, p = 3.90 × 10), with the dominant model being preferred. For rs2284038, the recessive model was preferred (OR = 1.18, 95% CI: 1.00-1.40, p = 4.76 × 10), whereas analysis of dominant model showed no association (OR = 1.10, 95% CI: 0.98-1.22, p = 0.10).
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.
最近一项研究发现，位于22q12.3的C1QTNF6基因、22q13.1的RAC2基因以及14q32.2的一个基因间区域内的变异与格雷夫斯病（GD）风险相关。我们旨在在一个独立的汉族人群样本集中验证这些与GD的关联。
我们通过对位于这三个区域的最显著相关单核苷酸多态性（SNP）进行基因分型来研究这些关联。选择14q32.2基因间区域内的Rs1456988、22q12.3的C1QTNF6内的rs229527以及22q13.1的RAC2内的rs2284038进行基因分型。这三个SNP通过一项病例对照研究进行基因分型，该研究纳入了2382例GD患者和3092名来自中国北方汉族血统的无亲缘关系健康对照。基因分型在ABI7900平台上使用TaqMan分析进行。
我们发现C1QTNF6内的rs229527等位基因（优势比[OR]=1.23，置信区间[95%CI]：1.12 - 1.33，p = 4.60×10）以及RAC2内的rs2284038等位基因（OR = 1.10，95%CI：1.01 - 0.19，p = 3.00×10）均与GD易感性显著相关。然而，位于14q32.2的rs1456988（OR = 1.08，95%CI：0.99 - 1.16，p = 7.01×10）未显示出关联。遗传模型分析表明，rs229527的显性和隐性模型均显示出显著关联（OR = 1.24，95%CI：1.13 - 1.38，p = 9.90×10；OR = 1.49，95%CI：1.19 - 1.86，p = 3.90×10），显性模型更优。对于rs2284038，隐性模型更优（OR = 1.18，95%CI：1.00 - 1.40，p = 4.76×10），而显性模型分析未显示出关联（OR = 1.10，95%CI：0.98 - 1.22，p = 0.10）。
我们的研究结果证实，在一个独立的汉族人群中，22号染色体q12.3和q13.1区域的变异与GD相关；然而，14q32.2与GD无关联。
