1. ¹INSERM, U582, Institut de Myologie, Paris, France
2. ²Université Pierre et Marie Curie-Paris 6, UMR S582, IFR14, Paris, France
3. ³INSERM, UMRS 525, Université Pierre et Marie Curie-Paris 6, Paris, France
4. ⁴INSERM U780, IFR 69, Villejuif, France
5. ⁵IRSA, La Riche, France
6. ⁶AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Biochimie, Paris, France

Correspondence: Dr L Gouas, Service de Cytogénétique Médicale, Faculté de Médecine et de Pharmacie, 28 place Henri Dunant, 63001 Clermont-Ferrand Cedex, France. Tel: + 33 4 73 17 81 00; Fax: + 33 4 73 26 91 82; E-mail: lgouas@chu-clermontferrand.fr

Received 30 November 2006; Revised 26 April 2007; Accepted 2 May 2007; Published online 30 May 2007.

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 rs1805123 (K897 T) and rs3815459, SCN5A rs1805126 (D1819D), 1141-3 C>A, rs1805124 (H558R), and IVS24+116 G>A, KCNQ1 rs757092, KCNE1 IVS2-128 G>A and rs1805127 (G38S), and KCNE2 rs2234916 (T8A)). However, few of these results have been replicated in independent populations. We tested the association of SNPs KCNQ1 rs757092, KCNH2 rs3815459, SCN5A IVS24+116 G>A, KCNE1 IVS2-128 G>A and KCNE2 rs2234916 with QTc length in two groups of 200 subjects presenting the shortest and the longest QTc from a cohort of 2008 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 rs757092 G and KCNH2 rs3815459 A were more frequent in the group with the longest QTc. There was no significant difference for KCNE1 IVS2-128 G>A and KCNE2 rs2234916 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 (rs2236609) and rs1805127 (G38S), respectively. In conclusion, our study confirms the reported associations between QTc length and KCNQ1 rs757092 and KCNH2 rs3815459.