Details

Autor(en) / Beteiligte

• AARNOUDSE, Albert-Jan L. H. J
• NEWTON-CHEH, Christopher
• DE BAKKER, Paul I. W
• STRAUS, Sabine M. J. M
• KORS, Jan A
• HOFMAN, Albert
• UITTERLINDEN, André G
• WITTEMAN, Jacqueline C. M
• STRICKER, Bruno H. C

Titel

Common NOS1AP variants are associated with a prolonged QTc interval in the rotterdam study

Ist Teil von

• Circulation (New York, N.Y.), 2007-07, Vol.116 (1), p.10-16

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• QT prolongation is an important risk factor for sudden cardiac death. About 35% of QT-interval variation is heritable. In a recent genome-wide association study, a common variant (rs10494366) in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene was found to be associated with QT-interval variation. We tested for association of 2 NOS1AP variants with QT duration and sudden cardiac death. The Rotterdam Study is a population-based, prospective cohort study of individuals > or = 55 years of age. The NOS1AP variants rs10494366 T>G and rs10918594 C>G were genotyped in 6571 individuals. Heart rate-corrected QT interval (QTc) was determined with ECG analysis software on up to 3 digital ECGs per individual (total, 11,108 ECGs from 5374 individuals). The association with QTc duration was estimated with repeated-measures analyses, and the association with sudden cardiac death was estimated by Cox proportional-hazards analyses. The rs10494366 G allele (36% frequency) was associated with a 3.8-ms (95% confidence interval, 3.0 to 4.6; P=7.8x10(-20)) increase in QTc interval duration for each additional allele copy, and the rs10918594 G allele (31% frequency) was associated with a 3.6-ms (95% confidence interval, 2.7 to 4.4; P=6.9x10(-17)) increase per additional allele copy. None of the inferred NOS1AP haplotypes showed a stronger effect than the individual single-nucleotide polymorphisms. There were 233 sudden cardiac deaths over 11.9 median years of follow-up. No significant association was observed with sudden cardiac death risk. Common variants in NOS1AP are strongly associated with QT-interval duration in an elderly population. Larger sample sizes are needed to confirm or exclude an effect on sudden cardiac death risk.