A common variant in SLC8A1 is associated with the duration of the electrocardiographic QT interval.
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.
Center for Genome Science, National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong, Korea.
Jong Wook
JW
Kim
Kyung-Won
KW
Hong
Min Jin
MJ
Go
Sung Soo
SS
Kim
Yasuharu
Y
Tabara
Yoshikuni
Y
Kita
Takeshi
T
Tanigawa
Yoon Shin
YS
Cho
Bok-Ghee
BG
Han
Bermseok
B
Oh
D000328:Adult; D000368:Aged; D004562:Electrocardiography; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019831:Sodium-Calcium Exchanger / Q000235:genetics*; D054928:Validation Studies as Topic
D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1