Association of single nucleotide polymorphic variants of the <i>NOS1AP</i> gene with QT interval duration

Abstract

Highlights. The association of single nucleotide polymorphic variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval was found in men of the Siberian population.Aim. To study the association of single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval.Methods. The study sample of men (1353 people) aged 25–69 years was formed from the DNA bank of participants in the international HAPIEE project and screening of young people 25–44 years old, residents of Novosibirsk. From each age subgroup (25–29, 30–34, …, 65–69 years old), about 10–15% of men with the shortest, average and longest QT interval were selected and the corresponding groups were formed. Genotyping of rs4657139 was carried out using PCR with RFLP (polymerase chain reaction followed by restriction fragment length polymorphism analysis). Genotyping rs12143842 – using RT-PCR (real-time polymerase chain reaction).Results. At the age of over 50 years, the CC genotype rs12143842 was detected in 66.1% of men in the group with a short and average QT interval and in 50.6% in the group with a long QT interval, while the TT genotype prevailed in the group with a long QT interval, 10, 8% of cases (odds ratio (OR) = 3.345, 95% confidence interval (CI) 1.149–9.739, p = 0.02). The homozygous TT genotype rs4657139 was more common in the long QT group, in 20.1% of cases, while the AA and AT genotypes predominated in the short, average QT groups (p = 0.041). A similar trend persists when separating by age in people over 50 years of age (p = 0.031) and when comparing genotype frequencies in the long and average QT groups in the model TT vs AA + AT & long QT vs short + average QT (p = 0.003).Conclusion. Single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene are associated with the duration of the QT interval in male residents of Novosibirsk.