Gouas L, Nicaud V, Chaouch S, Berthet M, Forhan A, Tichet J, Tiret L, Balkau B, Guicheney P
INSERM, U582, Institut de Myologie, Paris, France.
Eur J Hum Genet. 2007 Sep;15(9):974-9. doi: 10.1038/sj.ejhg.5201866. Epub 2007 May 30.
Population-based association studies have identified several polymorphic variants in genes encoding ion channel subunits associated with the electrocardiographic heart-rate-corrected QT (QTc) length in healthy populations of Caucasian origin (KCNH2 rs1,805,123 (K897 T) and rs3,815,459, SCN5A rs1,805,126 (D1,819D), 1,141-3 C>A, rs1,805,124 (H558R), and IVS24+116 G>A, KCNQ1 rs757,092, KCNE1 IVS2-128 G>A and rs1,805,127 (G38S), and KCNE2 rs2,234,916 (T8A)). However, few of these results have been replicated in independent populations. We tested the association of SNPs KCNQ1 rs757,092, KCNH2 rs3,815,459, SCN5A IVS24+116 G>A, KCNE1 IVS2-128 G>A and KCNE2 rs2,234,916 with QTc length in two groups of 200 subjects presenting the shortest and the longest QTc from a cohort of 2,008 healthy subjects. All polymorphisms were in Hardy-Weinberg equilibrium in both groups. The minor allele SCN5A IVS24+116 A was more frequent in the group of subjects with the shortest QTc, whereas the minor alleles KCNQ1 rs757,092 G and KCNH2 rs3,815,459 A were more frequent in the group with the longest QTc. There was no significant difference for KCNE1 IVS2-128 G>A and KCNE2 rs2,234,916 between the two groups. Haplotype analysis showed a twofold increased risk of QTc lengthening for carriers of the haplotype, combining alleles C and A of the two common KCNE1 SNPs, IVS2-129 C>T (rs2,236,609) and rs1,805,127 (G38S), respectively. In conclusion, our study confirms the reported associations between QTc length and KCNQ1 rs757,092 and KCNH2 rs3,815,459.
基于人群的关联研究已经在编码离子通道亚基的基因中鉴定出了几种多态性变体，这些变体与白种人健康人群的心电图心率校正QT（QTc）长度相关（KCNH2 rs1805123（K897T）和rs3815459，SCN5A rs1805126（D1819D），1141 - 3 C>A，rs1805124（H558R），以及IVS24 + 116 G>A，KCNQ1 rs757092，KCNE1 IVS2 - 128 G>A和rs1805127（G38S），以及KCNE2 rs2234916（T8A））。然而，这些结果中很少能在独立人群中得到重复验证。我们在两组各200名受试者中测试了单核苷酸多态性（SNP）KCNQ1 rs757092、KCNH2 rs3815459、SCN5A IVS24 + 116 G>A、KCNE1 IVS2 - 128 G>A和KCNE2 rs2234916与QTc长度的关联，这两组受试者分别来自2008名健康受试者队列中QTc最短和最长的人群。两组中所有多态性均处于哈迪 - 温伯格平衡。SCN5A IVS24 + 116 A次要等位基因在QTc最短的受试者组中更为常见，而KCNQ1 rs757092 G和KCNH2 rs3815459 A次要等位基因在QTc最长的受试者组中更为常见。两组之间KCNE1 IVS2 - 128 G>A和KCNE2 rs2234916没有显著差异。单倍型分析显示，携带分别结合了两个常见KCNE1 SNP（IVS2 - 129 C>T（rs2236609）和rs1805127（G38S））的C和A等位基因的单倍型的携带者，QTc延长风险增加了两倍。总之，我们的研究证实了所报道的QTc长度与KCNQ1 rs757092和KCNH2 rs3815459之间的关联。
