{{Rsnum
|rsid=10494366
|Gene=NOS1AP
|Chromosome=1
|position=162115895
|Orientation=plus
|GMAF=0.4761
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
|Gene_s=NOS1AP
}}{{ population diversity
| geno1=(G;G)
| geno2=(G;T)
| geno3=(T;T)
| CEU | 10.6 | 48.7 | 40.7
| HCB | 46.7 | 38.7 | 14.6
| JPT | 46.9 | 43.4 | 9.7
| YRI | 46.9 | 45.6 | 7.5
| ASW | 40.4 | 47.4 | 12.3
| CHB | 46.7 | 38.7 | 14.6
| CHD | 45.9 | 44.0 | 10.1
| GIH | 58.4 | 32.7 | 8.9
| LWK | 61.8 | 29.1 | 9.1
| MEX | 17.2 | 39.7 | 43.1
| MKK | 36.5 | 46.8 | 16.7
| TSI | 9.8 | 44.1 | 46.1
| HapMapRevision=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|OA=1
}} [[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 Summary
|SNP=rs10494366
|PubMedID=16648850
|Condition=QT interval prolongation
|Gene=NOS1AP
|Risk Allele=
|pValue=1.00E-010
|OR=4.9
|95CI= 7.90 (NR) msec difference between homozygote
}}

{{PMID Auto
|PMID=19247217
|Title=Calcium channel blockers, NOS1AP, and heart-rate-corrected QT prolongation
}}

{{omim
|desc=QT INTERVAL, VARIATION IN
|id=610141
|rsnum=10494366
}}

{{PMID Auto
|PMID=19943157
|Title=NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study
|OA=1
}}

{{PharmGKB
|RSID=rs10494366
|Name_s=
|Gene_s=NOS1AP
|Feature=
|Evidence=PubMed ID:19247217
|Annotation=In a study of 112 patients taking verapamil, patients carrying genotype GG of this SNP showed significantly more QTc prolongation than users with the TT genotype. Genotype at this SNP was not significantly associated with QTc prolongation in the 44 patients studied who were taking isradipine.
|Drugs=isradipine; verapamil
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA163993332
}}

{{PMID Auto
|PMID=19289301
|Title=SNP association and sequence analysis of the NOS1AP gene in SIDS
}}

{{PMID Auto GWAS
|PMID=20062063
|Trait=Electrocardiographic traits
|Title=Several common variants modulate heart rate, PR interval and QRS duration
|RiskAllele=G
|Pval=5E-22
|OR=12.20
|ORtxt=[9.72-14.68] % SD increase
}}

{{PMID Auto
|PMID=20215044
|Title=Relationship of Common Candidate Gene Variants to Electrocardiographic T-Wave Peak to T-Wave End Interval and T-Wave Morphology Parameters
|OA=1
}}

{{PMID Auto
|PMID=20538168
|Title=Polymorphisms in the NOS1AP Gene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome
}}
{{PMID Auto
|PMID=20722683
|Title=A common variant of NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes
|OA=1
}}

{{PharmGKB
|RSID=rs10494366
|Name_s=
|Gene_s=NOS1AP
|Feature=
|Evidence=PubMed ID:16648850; PubMed ID:17565224; PubMed ID:17576865; PubMed ID:18511491
|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.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA161748484
}}

{{PharmGKB
|RSID=rs10494366
|Name_s=
|Gene_s=NOS1AP
|Feature=
|Evidence=PubMed ID:18927126
|Annotation=This common variant is associated with QT interval duration in genome-wide association studies.
|Drugs=
|Drug Classes=
|Diseases=Long QT Syndrome
|Curation Level=Curated
|PharmGKB Accession ID=PA162356020
}}

{{PharmGKB
|RSID=rs10494366
|Name_s=
|Gene_s=NOS1AP
|Feature=
|Evidence=PubMed ID:16648850; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization (Initial Sample Size: 100 > 445ms, 100 < 386ms; Replication Sample Size: 200 > 85th pct, 200 < 15th pct, 7,817 cohort members). This variant is associated with QT interval prolongation.
|Drugs=
|Drug Classes=
|Diseases=Acquired Long QT Syndrome (aLQTS); congenital long QT syndrome; Long QT Syndrome
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA162356360
}}

{{PMID Auto
|PMID=21663814
|Title=5 HT(3)-receptor antagonists and cardiac repolarization time in patients expressing a novel genetic target associated with baseline QTc interval abnormalities
}}

{{PMID Auto
|PMID=22133205
|Title=Allelic variant of NOS1AP effects on cardiac alternans of repolarization during exercise testing
}}

{{PMID Auto
|PMID=17903306
|Title=Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study.
|OA=1
}}

{{PMID Auto
|PMID=18785031
|Title=Common variation in NOS1AP and KCNH2 genes and QT interval duration in young adults. The Cardiovascular Risk in Young Finns Study.
}}

{{PMID Auto
|PMID=18852197
|Title=Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
|OA=1
}}

{{PMID Auto
|PMID=19019189
|Title=Common candidate gene variants are associated with QT interval duration in the general population.
|OA=1
}}

{{PMID Auto
|PMID=19076153
|Title=A common NOS1AP genetic polymorphism is associated with increased cardiovascular mortality in users of dihydropyridine calcium channel blockers.
|OA=1
}}

{{PMID Auto
|PMID=19180230
|Title=Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.
|OA=1
}}

{{PMID Auto
|PMID=19305408
|Title=Common variants at ten loci influence QT interval duration in the QTGEN Study.
|OA=1
}}

{{PMID Auto
|PMID=19389826
|Title=Linkage disequilibrium mapping of the replicated type 2 diabetes linkage signal on chromosome 1q.
|OA=1
}}

{{PMID Auto
|PMID=19587794
|Title=Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies.
|OA=1
}}

{{PMID Auto
|PMID=20031603
|Title=A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project.
|OA=1
}}

{{PMID Auto
|PMID=20305679
|Title=A variation in NOS1AP gene is associated with repaglinide efficacy on insulin resistance in type 2 diabetes of Chinese.
|OA=1
}}

{{PMID Auto
|PMID=22019493
|Title=Cardiac levels of NOS1AP RNA from right ventricular tissue recovered during lead extraction.
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs10494366
|overall_frequency_n=56
|overall_frequency_d=128
|overall_frequency=0.4375
|n_genomes=35
|n_genomes_annotated=0
|n_haplomes=47
|n_articles=2
|n_articles_annotated=1
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}