Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes.
Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes.
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DOI：
10.1001/jama.2008.649
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发表时间：
2008-11-26
影响因子：
120.7
通讯作者：
Warram, James H.
中科院分区：
文献类型：
--
作者：
Doria, Alessandro;Wojcik, Joanna;Xu, Rui;Gervino, Ernest V.;Hauser, Thomas H.;Johnstone, Michael T.;Nolan, David;Hu, Frank B.;Warram, James H.
A common allele on chromosome 9p21 has been repeatedly associated with increased risk of coronary artery disease (CAD) in the general population. However, the magnitude of this effect in the population with diabetes has not been well characterized. To examine the association of the 9p21 variant with CAD in individuals with type 2 diabetes and evaluate its interaction with poor glycemic control. 1. Case-control study of 734 type 2 diabetic patients (322 with angiographically-diagnosed CAD and 412 with no evidence of CAD) who were recruited in 2001–2006 at the Joslin Clinic/Beth Israel Deaconess Medical Center, 2. Independent cohort study of 475 type 2 diabetic patients from the Joslin Clinic whose survival status was monitored from their recruitment in 1993–1996 until December 31, 2004. Study subjects were genotyped for a representative SNP at 9p21 (rs2383206) and characterized for their long-term glycemic control by averaging multiple hemoglobin A1c (HbA1c) measurements taken in the years before study entry. Case-control study: association between SNP rs2383206 and CAD defined as angiographically documented stenosis greater than 50% in a major coronary artery or a main branch thereof. Cohort study: cumulative 10-year mortality. Individuals homozygous for the risk allele were significantly more frequent in case than control subjects (42.3 vs. 28.9%, p=0.0002). This association was unaffected by adjustment for cardiovascular risk factors, but the effect of the risk genotype was significantly magnified (adjusted p for interaction = 0.048) in the presence of poor glycemic control (worst tertile of the distribution of HbA1c at examination). Relative to the CAD risk for patients with neither a 9p21 risk allele nor poor glycemic control, the CAD risk for subjects having two risk alleles but not poor glycemic control was increased two-fold (OR=1.99, 1.17–3.41), whereas the risk for study subjects with the same genotype and with poor glycemic control was increased four-fold (OR=4.27, 2.26–8.01). The interaction was stronger (adjusted p=0.005) when a measure of long-term glycemic control (7-year average rather than most recent HbA1c) was used, with ORs of 7.83 (3.49–17.6) for subjects having two risk alleles and a history of poor glycemia and 1.54 (0.72–3.30) for subjects with the same genotype but without this exposure. A similar interaction between 9p21 variant and poor glycemic control was observed with respect to cumulative 10-year mortality in the cohort study (43.6% in patients with two risk alleles and poor glycemic control, 23.1% in those with only the two risk alleles, 30.0% in those with only poor glycemic control, and 31.6% in those with neither factor, p for interaction=0.036). In this study population, the CAD risk associated with the 9p21 variant was increased in the presence of poor glycemic control in type 2 diabetes.
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DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
7.7
作者：
Boonyasrisawat, Watip;Eberle, Delphine;Doria, Alessandro
通讯作者：
Doria, Alessandro
影响因子：
30.8
作者：
Helgadottir, Anna;Thorleifsson, Gudmar;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
3.5
作者：
Lacquemant, C;Froguel, P;Ruiz, J
通讯作者：
Ruiz, J
DOI：
10.1016/s0735-1097(02)02164-2
发表时间：
2002-10-16
影响因子：
24
作者：
Gibbons, RJ;Balady, GJ;Smith, SC
通讯作者：
Smith, SC