title: Confirmation of associations between ion channel gene SNPs and QTc interval duration in healthy subjects.
abstract: 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.
authors.affiliation: INSERM, U582, Institut de Myologie, Paris, France. lgouas@chu-clermontferrand.fr
authors.forename: L
authors.initials: L
authors.lastname: Gouas
authors.forename: V
authors.initials: V
authors.lastname: Nicaud
authors.forename: S
authors.initials: S
authors.lastname: Chaouch
authors.forename: M
authors.initials: M
authors.lastname: Berthet
authors.forename: A
authors.initials: A
authors.lastname: Forhan
authors.forename: J
authors.initials: J
authors.lastname: Tichet
authors.forename: L
authors.initials: L
authors.lastname: Tiret
authors.forename: B
authors.initials: B
authors.lastname: Balkau
authors.forename: P
authors.initials: P
authors.lastname: Guicheney
mesh_terms: D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D006239:Haplotypes; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016276:Ventricular Function / Q000235:genetics*
chemical_list: D007473:Ion Channels