NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study.
NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study.
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DOI：
10.1007/s00125-009-1608-0
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发表时间：
2010-03
期刊：
影响因子：
8.2
通讯作者：
Kao, W. H. L.
中科院分区：
文献类型：
--
作者：
Chu, A. Y.;Coresh, J.;Arking, D. E.;Pankow, J. S.;Tomaselli, G. F.;Chakravarti, A.;Post, W. S.;Spooner, P. H.;Boerwinkle, E.;Kao, W. H. L.
验证NOS 1AP（编码一氧化氮合酶-1衔接蛋白的基因）中rs 10494366与钙通道阻滞剂（CCB）使用者2型糖尿病发病率之间的相关性，并确定与2型糖尿病风险相关的其他NOS 1AP变体。分析了来自社区动脉粥样硬化风险研究的9，221名中年白色和2，724名非裔美国人基线无糖尿病的9年随访数据。根据基线CCB使用分层，研究了19种NOS 1AP变异与糖尿病发病率和空腹血糖水平的相关性。基线时CCB使用率在白人中为2.7%（n= 247），在非裔美国人中为2.3%（n=72）。在白色CCB使用者中，rs 10494366的G等位基因与较低的糖尿病发病率相关（HR 0.57，95% CI 0.35-0.92，p=0.016）。在调整年龄、性别、肥胖、吸烟、饮酒、体力活动、高血压、心率和心电图QT间期后，该相关性略显着（HR 0.63，95% CI 0.38-1.04，p=0.052）。rs 10494366与随访期间较低的平均空腹血糖相关（p=0.037）。经过多次测试纠正后，没有其他变异与CCB使用者的糖尿病风险相关。在非CCB使用者中未观察到任何NOS 1AP变异与糖尿病发展之间的关联。在非裔美国人CCB使用者或非CCB使用者中，NOS 1AP变异与糖尿病风险无关。我们在白色CCB使用者中独立复制了NOS 1AP中rs 10494366与糖尿病事件之间的关联。进一步探索NOS 1AP变异与2型糖尿病的关系以及NOS 1AP在2型糖尿病病理中的功能研究是必要的。
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. 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. 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. 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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影响因子：
7.7
作者：
Duncan, BB;Schmidt, MI;Heiss, G
通讯作者：
Heiss, G
影响因子：
9.8
作者：
Hanson, RL;Ehm, MG;Knowler, WC
通讯作者：
Knowler, WC
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
DOI：
10.1073/pnas.0709118105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Chang, Kuan-Cheng;Barth, Andreas S.;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
7.7
作者：
Prokopenko I;Zeggini E;Hanson RL;Mitchell BD;Rayner NW;Akan P;Baier L;Das SK;Elliott KS;Fu M;Frayling TM;Groves CJ;Gwilliam R;Scott LJ;Voight BF;Hattersley AT;Hu C;Morris AD;Ng M;Palmer CN;Tello-Ruiz M;Vaxillaire M;Wang CR;Stein L;Chan J;Jia W;Froguel P;Elbein SC;Deloukas P;Bogardus C;Shuldiner AR;McCarthy MI;International Type 2 Diabetes 1q Consortium
通讯作者：
International Type 2 Diabetes 1q Consortium