Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, China.
Nat Genet. 2012 Sep;44(9):1026-9. doi: 10.1038/ng.2367. Epub 2012 Aug 5.
Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of thyrotoxicosis. We conducted a genome-wide association study (GWAS) and a replication study with a total of 123 southern Chinese with TPP (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; P(meta-analysis) = 1.8 × 10(-14)). All subjects with TPP also had Graves' disease, and subsequent TPP versus Graves' disease comparison confirmed that the association at 17q24.3 was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk prediction of TPP in subjects with Graves' disease was 0.73. Expression quantitative trait locus (eQTL) analysis identified SNPs in the region flanking rs312691 (±10 kb) that could potentially affect KCNJ2 expression (P = 0.0001). Our study has identified a susceptibility locus associated with TPP and provides insight into the causes of TPP.
毒性弥漫性甲状腺肿伴周期性瘫痪（TPP）是甲状腺毒症的一种潜在危及生命的并发症。我们进行了一项全基因组关联研究（GWAS）和一项共纳入 123 名中国南方 TPP 患者（病例）和 1170 名健康对照的复制研究，在染色体 17q24.3 附近的 KCNJ2 基因（rs312691：比值比（OR）=3.3；P（荟萃分析）=1.8×10(-14))）上发现了一个易感位点。所有 TPP 患者均患有格雷夫斯病，随后进行的 TPP 与格雷夫斯病比较证实，17q24.3 上的关联仅与 TPP 相关。在格雷夫斯病患者中，rs312691 基因型对 TPP 风险预测的曲线下面积（AUC）为 0.73。表达数量性状基因座（eQTL）分析确定了 rs312691 侧翼区域（±10 kb）的 SNPs，这些 SNPs 可能影响 KCNJ2 的表达（P=0.0001）。本研究确定了与 TPP 相关的易感位点，为 TPP 的病因提供了新的见解。
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