Several polymorphisms of KCNQ1 gene are associated with plasma lipid levels in general Chinese populations.
Several polymorphisms of KCNQ1 gene are associated with plasma lipid levels in general Chinese populations.
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DOI：
10.1371/journal.pone.0034229
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang XF
中科院分区：
文献类型：
--
作者：
Chen XD;Yang YJ;Li SY;Peng QQ;Zheng LJ;Jin L;Wang XF
钾电压门控通道KQT样亚家族成员1（KCNQ 1）被认为是糖尿病的重要候选基因。在最近的全基因组关联研究中，在其内含子15中的40 kb连锁不平衡（LD）块中的几个单核苷酸多态性（SNP）已被确定与东亚人群中的糖尿病相关。本研究旨在探讨KCNQ 1基因多态性是否影响中国普通人群的代谢表型水平。我们调查了上述40 kb LD区块中的两个SNP（rs 2237892和rs 2237895）、外显子10中的错义变体rs 12720449（P448 R）和外显子13中的同义变体rs 1057128（S546 S）与维吾尔族人群（n = 478）代谢表型的关联，并在汉族人群（n = 2,485）中复制了这些关联。 我们发现rs 2237892-T等位基因与甘油三酯水平降低显著相关（pcombined = 0.001）。 rs 12720449的次要G等位基因在欧洲和东亚人群中的等位基因频率存在显著差异（分别为0.2%和14%），在维吾尔族受试者（p = 0.004）、汉族受试者（p = 0.052）和荟萃分析受试者（pcombined = 0.001）中，G等位基因与甘油三酯水平低于G等位基因相关。 此外，在荟萃分析中，rs 1057128的次要A等位基因也与甘油三酯水平降低相关（pcombined = 0.010）。 据我们所知，这是第一份将KCNQ 1的错义突变rs 12720449与甘油三酯水平相关联的报告。Rs 2237892代表40-kb LD阻断，也与汉族人群中的甘油三酯水平相关。需要进一步的研究在其他东亚人群中复制这些发现。
Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) is thought to be an important candidate gene of diabetes. Several single nucleotide polymorphisms (SNPs) in a 40-kb linkage disequilibrium (LD) block in its intron 15 have been identified to be associated with diabetes in East Asian populations in recent genome-wide association studies. The aim of this study was to investigate whether KCNQ1 polymorphisms influence the levels of the metabolic phenotypes in general Chinese populations. We investigated the associations of two SNPs (rs2237892 and rs2237895) in the aforementioned 40-kb LD block, a missense variant rs12720449 (P448R) in exon 10, and a synonymous variant rs1057128 (S546S) in exon 13 with metabolic phenotypes in a Uyghur population (n = 478) and replicated these associations in a Han population (n = 2,485). We found that rs2237892-T allele was significantly associated with decreased triglyceride levels (pcombined = 0.001). The minor G allele of the rs12720449, with sharp difference of the allelic frequency between European and East Asian populations (0.2% versus 14%, respectively), was associated with a lower triglyceride levels than G allele in Uyghur subjects (p = 0.004), in Han subjects (p = 0.052), and in subjects of meta-analysis (pcombined = 0.001). Moreover, the minor A allele of the rs1057128 was also associated with decreased triglyceride levels in meta-analysis (pcombined = 0.010). To the best of our knowledge, this is the first report associating a missense mutation of KCNQ1, rs12720449, with triglyceride levels. Rs2237892, representing the 40-kb LD block, is also associated with triglyceride levels in Han population. Further studies are required to replicate these findings in other East Asian populations.
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