rs10494366

plus

Geno	Mag	Summary
(G;G)		Long QT interval
(G;T)	0	average QT interval
(T;T)	2	Shorter QT interval

Reference

GRCh38 38.1/141

Chromosome

1

Position

162115895

Gene	LOC105371475, NOS1AP

is a	snp
is	mentioned by
dbSNP	rs10494366
dbSNP (classic)	rs10494366
ClinGen	rs10494366
ebi	rs10494366
HLI	rs10494366
Exac	rs10494366
Gnomad	rs10494366
Varsome	rs10494366
LitVar	rs10494366
Map	rs10494366
PheGenI	rs10494366
Biobank	rs10494366
1000 genomes	rs10494366
hgdp	rs10494366
ensembl	rs10494366
geneview	rs10494366
scholar	rs10494366
google	rs10494366
pharmgkb	rs10494366
gwascentral	rs10494366
openSNP	rs10494366
23andMe	rs10494366
SNPshot	rs10494366
SNPdbe	rs10494366
MSV3d	rs10494366
GWAS Ctlg	rs10494366

GMAF

0.4761

Max Magnitude

2

?

(G;G) (G;T) (T;T)

28

rs10494366, a SNP in the NOS1AP gene encoding the nitric oxide synthase I adaptor protein, accounts for some of the variation seen in abnormal heart rhythms, in particular, the QT interval. Based on studies totaling ~4,000 individuals of Caucasian ancestry, homozygotes for one allele have shorter QT intervals, while homozygotes for the other allele have a longer QT interval. [PMID 16648850]

A follow-up study determined that one rs10494366(G) allele was associated with a 3.8-ms (CI: 3.0 - 4.6ms, p=7.8x10(-20)) increase in QT interval duration, and two (G) alleles had twice that increase. No increase in risk for sudden death due to a cardiac problem was associated with this SNP, though. [PMID 17576865]

[PMID 18235038 ] rs10494366 minor homozygotes had a 9.3 msec longer QT interval compared to major homozygotes (p=5.7x10(-5)); rs10918594 minor homozygotes had a 12.5 msec longer QT interval compared to major homozygotes (p=1.5x10(-6)). Restricting analyses to the diabetic EAs strengthened the effect despite the reduction in sample size (11.3 msec difference, p=5.1x10(-5); 13.9 msec difference, p=1.6x10(-6), respectively).

[PMID 18551039] Patients with rs10494366(G;T) or (G;G) genotypes have an increased mortality risk (hazard ratio 2.8) compared to (T;T) genotypes upon treatment with sulfonylurea antidiabetic drugs. Glibenclamide is less effective in reducing glucose levels and mortality rates were higher compared with glibenclamide users with the (T;T) genotype. However, in tolbutamide and glimepiride users, the (G;T) and (G;G) genotypes were associated with a reduced mortality rate.

[PMID 19204306 ] rs10494366, rs4657139 and rs16847548 were significantly associated with adjusted QT interval in whites. relative hazard of SCD associated with each C allele at rs16847548 was 1.31. rs12567209 was also independently associated with SCD in whites (relative hazard 0.57, 95% confidence interval 0.39 to 0.83, P=0.003). No significant associations observed in blacks.

GWAS
SNP	rs10494366
PubMedID	[PMID 16648850]
Condition	QT interval prolongation
Gene	NOS1AP
Risk Allele
pValue	1.00E-010
OR	4.9
95% CI	7.90 (NR) msec difference between homozygote

[PMID 19247217] Calcium channel blockers, NOS1AP, and heart-rate-corrected QT prolongation

OMIM	610141
Desc	QT INTERVAL, VARIATION IN
Variant
Related	also

[PMID 19943157 ] NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study

[PMID 19289301] SNP association and sequence analysis of the NOS1AP gene in SIDS

GWAS snp
PMID	[PMID 20062063]
Trait	Electrocardiographic traits
Title	Several common variants modulate heart rate, PR interval and QRS duration
Risk Allele	G
P-val	5E-22
Odds Ratio	12.20 [9.72-14.68] % SD increase

[PMID 20215044 ] Relationship of Common Candidate Gene Variants to Electrocardiographic T-Wave Peak to T-Wave End Interval and T-Wave Morphology Parameters

[PMID 20538168] Polymorphisms in the NOS1AP Gene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome

[PMID 20722683 ] A common variant of NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes

[PMID 21663814] 5 HT(3)-receptor antagonists and cardiac repolarization time in patients expressing a novel genetic target associated with baseline QTc interval abnormalities

[PMID 22133205] Allelic variant of NOS1AP effects on cardiac alternans of repolarization during exercise testing

[PMID 17903306 ] Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study.

[PMID 18785031] Common variation in NOS1AP and KCNH2 genes and QT interval duration in young adults. The Cardiovascular Risk in Young Finns Study.

[PMID 18852197 ] Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.

[PMID 19019189 ] Common candidate gene variants are associated with QT interval duration in the general population.

[PMID 19076153 ] A common NOS1AP genetic polymorphism is associated with increased cardiovascular mortality in users of dihydropyridine calcium channel blockers.

[PMID 19180230 ] Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.

[PMID 19305408 ] Common variants at ten loci influence QT interval duration in the QTGEN Study.

[PMID 19389826 ] Linkage disequilibrium mapping of the replicated type 2 diabetes linkage signal on chromosome 1q.

[PMID 19587794 ] Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies.

[PMID 20031603 ] A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project.

[PMID 20305679 ] A variation in NOS1AP gene is associated with repaglinide efficacy on insulin resistance in type 2 diabetes of Chinese.

[PMID 22019493] Cardiac levels of NOS1AP RNA from right ventricular tissue recovered during lead extraction.

[PMID 25819866] Genetic markers of repolarization and arrhythmic events after acute coronary syndromes

[PMID 26332198] NOS1AP polymorphisms modify QTc interval duration but not cardiac arrest risk in hypertrophic cardiomyopathy