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A common variant in SLC8A1 is associated with the duration of the electrocardiographic QT interval.

ABSTRACT: Prolongation of the electrocardiographic QT interval, a measure of cardiac repolarization, predisposes one to ventricular arrhythmias and sudden cardiac death. Since NOS1AP, a regulator of neuronal nitric oxide synthase, was discovered in a genome-wide association study (GWAS) as a novel target that modulates cardiac repolarization, several loci have been linked to the QT interval in studies (QTGEN and QTSCD) of European descendents. However, there has been no GWAS of the QT interval in Asian populations. We conducted a GWAS with regard to the QT interval in Korea Association Resource (KARE [n = 6,805]) cohorts. Replication studies in independent populations of Korean (n = 4,686) and Japanese (n = 2,687) groups validated the association between a SNP, rs13017846, which maps to near SLC8A1 (sodium/calcium exchanger 1 precursor, overall p = 8.0 × 10(-14)), and the QT interval. The minor allele frequency (MAF) of rs13017846 varies widely between ethnicities-0.053 in Europeans (HapMap CEU [Utah residents with ancestry from northern and western Europe from the Centre d'Étude du Polymorphisme Humain collection] samples) versus 0.080 in Africans (HapMap YRI [Yoruba in Ibadan, Nigeria] samples)-whereas a MAF of 0.500 has been reported in Asians (HapMap HCB [Han Chinese in Beijing, China] and JPT [Japanese in Tokyo, Japan] samples). This might explain why this locus has not been identified in Europeans in previous studies.

SUBMITTER: Kim JW

PROVIDER: S-EPMC3397256 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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A common variant in SLC8A1 is associated with the duration of the electrocardiographic QT interval.

Kim Jong Wook JW Hong Kyung-Won KW Go Min Jin MJ Kim Sung Soo SS Tabara Yasuharu Y Kita Yoshikuni Y Tanigawa Takeshi T Cho Yoon Shin YS Han Bok-Ghee BG Oh Bermseok B

American journal of human genetics 20120621 1

Prolongation of the electrocardiographic QT interval, a measure of cardiac repolarization, predisposes one to ventricular arrhythmias and sudden cardiac death. Since NOS1AP, a regulator of neuronal nitric oxide synthase, was discovered in a genome-wide association study (GWAS) as a novel target that modulates cardiac repolarization, several loci have been linked to the QT interval in studies (QTGEN and QTSCD) of European descendents. However, there has been no GWAS of the QT interval in Asian po ...[more]

PMID: 22726844

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Project description:ContextDisturbances in 25-hydroxyvitamin D, calcium, and phosphorus concentrations have been associated with increased risks of total and cardiovascular mortality. It is possible that changes in electrocardiographic QT interval duration may mediate these effects, but the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration has not been evaluated in general population samples.ObjectiveThe objective of the study was to evaluate the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration in two large samples of the U.S. general population.DesignThis study included cross-sectional analyses the Third National Health and Nutrition Survey (NHANES III) and the Atherosclerosis Risk in Communities (ARIC) study.SettingThe study was conducted in the general community.Patients or other participantsPatients included 7,312 men and women from NHANES III and 14,825 men and women from the ARIC study.InterventionsSerum 25-hydroxyvitamin D, total and ionized calcium, and inorganic phosphorus were measured in NHANES III, and serum total calcium and inorganic phosphorus were measured in ARIC.Main outcome measureQT interval duration was obtained from standard 12-lead electrocardiograms.ResultsIn NHANES III, the multivariate adjusted differences in average QT interval duration comparing the highest vs. the lowest quartiles of serum total calcium, ionized calcium, and phosphorus were -3.6 msec (-5.8 to -1.3; P for trend = 0.005), -5.4 msec (-7.4 to -3.5; P for trend <0.001), and 3.9 msec (2.0-5.9; P for trend <0.001), respectively. The corresponding differences in ARIC were -3.1 msec (-4.3 to -2.0; P for trend <0.001), -2.9 msec (-3.8 to -1.9; P for trend <0.001), and 2.3 msec (1.3-3.3; P for trend <0.001). No association was found between 25-hydroxyvitamin D concentrations and QT interval duration.ConclusionsIn two large samples of the general population, QT interval duration was inversely associated with the serum total and ionized calcium and positively associated with serum phosphorus.

Dataset Information

A common variant in SLC8A1 is associated with the duration of the electrocardiographic QT interval.

Publications

A common variant in SLC8A1 is associated with the duration of the electrocardiographic QT interval.

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