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

A. Y. Chu, J. Coresh, D. E. Arking, J. S. Pankow, Gordon F. Tomaselli, A. Chakravarti, W. S. Post, P. H. Spooner, E. Boerwinkle, W. H.L. Kao

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)510-516
Number of pages7
JournalDiabetologia
Volume53
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

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Calcium Channel Blockers
Nitric Oxide Synthase
Type 2 Diabetes Mellitus
Atherosclerosis
Incidence
Genes
Proteins
African Americans
Fasting
Glucose
Obesity
Heart Rate
Smoking
Alleles
Alcohols
Exercise
Pathology
Hypertension

Keywords

  • ARIC study
  • Calcium channel blockers
  • Gene-drug interaction
  • NOS1AP
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study. / Chu, A. Y.; Coresh, J.; Arking, D. E.; Pankow, J. S.; Tomaselli, Gordon F.; Chakravarti, A.; Post, W. S.; Spooner, P. H.; Boerwinkle, E.; Kao, W. H.L.

In: Diabetologia, Vol. 53, No. 3, 01.03.2010, p. 510-516.

Research output: Contribution to journalArticle

Chu, AY, Coresh, J, Arking, DE, Pankow, JS, Tomaselli, GF, Chakravarti, A, Post, WS, Spooner, PH, Boerwinkle, E & Kao, WHL 2010, 'NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study', Diabetologia, vol. 53, no. 3, pp. 510-516. https://doi.org/10.1007/s00125-009-1608-0
Chu, A. Y. ; Coresh, J. ; Arking, D. E. ; Pankow, J. S. ; Tomaselli, Gordon F. ; Chakravarti, A. ; Post, W. S. ; Spooner, P. H. ; Boerwinkle, E. ; Kao, W. H.L. / NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study. In: Diabetologia. 2010 ; Vol. 53, No. 3. pp. 510-516.
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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.",
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T1 - NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study

AU - Chu, A. Y.

AU - Coresh, J.

AU - Arking, D. E.

AU - Pankow, J. S.

AU - Tomaselli, Gordon F.

AU - Chakravarti, A.

AU - Post, W. S.

AU - Spooner, P. H.

AU - Boerwinkle, E.

AU - Kao, W. H.L.

PY - 2010/3/1

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N2 - 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.

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KW - ARIC study

KW - Calcium channel blockers

KW - Gene-drug interaction

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KW - Type 2 diabetes

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