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

TitleNOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study.
Publication TypeJournal Article
Year of Publication2010
AuthorsChu AY, Coresh J, Arking DE, Pankow JS, Tomaselli GF, Chakravarti A, Post WS, Spooner PH, Boerwinkle E, Kao WHL
JournalDiabetologia
Volume53
Issue3
Pagination510-6
Date Published2010 Mar
ISSN1432-0428
KeywordsAdult, African Americans, African Continental Ancestry Group, Atherosclerosis, Blood Glucose, Calcium Channel Blockers, Calcium Channels, Diabetes Mellitus, Type 2, Electrocardiography, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Humans, Incidence, Male, Middle Aged, Risk
Abstract

AIMS/HYPOTHESIS: To validate the reported association between rs10494366 in NOS1AP (the gene encoding nitric oxide synthase-1 adaptor protein) and the incidence of type 2 diabetes in calcium channel blocker (CCB) users and to identify additional NOS1AP variants associated with type 2 diabetes risk.

METHODS: Data from 9 years of follow-up in 9,221 middle-aged white and 2,724 African-American adults free of diabetes at baseline from the Atherosclerosis Risk in Communities study were analysed. Nineteen NOS1AP variants were examined for associations with incident diabetes and fasting glucose levels stratified by baseline CCB use.

RESULTS: Prevalence of CCB use at baseline was 2.7% (n = 247) in whites and 2.3% (n = 72) in African-Americans. Among white CCB users, the G allele of rs10494366 was associated with lower diabetes incidence (HR 0.57, 95% CI 0.35-0.92, p = 0.016). The association was marginally significant after adjusting for age, sex, obesity, smoking, alcohol use, physical activity, hypertension, heart rate and electrocardiographic QT interval (HR 0.63, 95% CI 0.38-1.04, p = 0.052). rs10494366 was associated with lower average fasting glucose during follow-up (p = 0.037). No other variants were associated with diabetes risk in CCB users after multiple-testing correction. No associations were observed between any NOS1AP variant and diabetes development in non-CCB users. NOS1AP variants were not associated with diabetes risk in either African-American CCB users or non-CCB users.

CONCLUSIONS/INTERPRETATION: We have independently replicated the association between rs10494366 in NOS1AP and incident diabetes among white CCB users. Further exploration of NOS1AP variants and type 2 diabetes and functional studies of NOS1AP in type 2 diabetes pathology is warranted.

DOI10.1007/s00125-009-1608-0
Alternate JournalDiabetologia
PubMed ID19943157
PubMed Central IDPMC3039128
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01 HC055022 / HC / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
T32 HL007024 / HL / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
T32 HL007024-35 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
T32-HL007024 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
T32 DK062707-09 / DK / NIDDK NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
T32-DK62707 / DK / NIDDK NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
T32 DK062707 / DK / NIDDK NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States