From SNPedia
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.
| ? | (G;G) (G;T) (T;T) |
|---|
 |
[PMID 19247217] Calcium channel blockers, NOS1AP, and heart-rate-corrected QT prolongation
[PMID 19943157] NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study
| PharmGKB | PA161748484 |
| Name | |
| Annotation | This variant in intron 1 of the NOS1AP gene has been associated with resting QTc in a genome-wide association scan and replicated in independent populations. |
| Gene | NOS1AP |
| Featue | |
| Evidence | PubMed ID:16648850; PubMed ID:17565224; PubMed ID:17576865; PubMed ID:18511491 |
| Drugs | |
| Diseases | |
| Curation Level | Curated |
[PMID 19289301] SNP association and sequence analysis of the NOS1AP gene in SIDS
