Haptoglobin Genotype Is a Consistent Marker of Coronary Heart Disease Risk Among Individuals With Elevated Glycosylated Hemoglobin

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:61

Article

Cahill, Leah E.¹  Levy, Andrew P.²  Chiuve, Stephanie E.^1,3,4  Jensen, Majken K.¹  Wang, Hong^5,6  Shara, Nawar M.^5,6  Blum, Shany²  Howard, Barbara V.^5,6  Pai, Jennifer K.^4,7,8  Mukamal, Kenneth J.⁹  Rexrode, Kathryn M.^3,4,7  Rimm, Eric B.^1,4,7,8 

[1] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[2] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel

[3] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

[5] MedStar Hlth Res Inst, Washington, DC USA

[6] Georgetown Howard Univ, Ctr Clin & Translat Sci, Washington, DC USA

[7] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[8] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[9] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA

关键词: acute myocardial infarction;    coronary disease;    epidemiology;    genetic association;    genotype;    glycoproteins;   

DOI  :  10.1016/j.jacc.2012.09.063

来源: Elsevier

【 摘 要 】

Objectives This study sought to investigate into the biologically plausible interaction between the common haptoglobin (Hp) polymorphism rs#72294371 and glycosylated hemoglobin (HbA(1c)) on risk of coronary heart disease (CHD). Background Studies of the association between the Hp polymorphism and CHD report inconsistent results. Individuals with the Hp2-2 genotype produce Hp proteins with an impaired ability to prevent oxidative injury caused by elevated HbA(1c). Methods HbA(1c) concentration and Hp genotype were determined for 407 CHD cases matched 1:1 to controls (from the NHS [Nurses' Health Study]) and in a replication cohort of 2,070 individuals who served as the nontreatment group in the ICARE (Prevention of Cardiovascular Complications in Diabetic Patients With Vitamin E Treatment) study, with 29 CHD events during follow-up. Multivariate models were adjusted for lifestyle and CHD risk factors as appropriate. A pooled analysis was conducted of NHS, ICARE, and the 1 previously published analysis (a cardiovascular disease case-control sample from the Strong Heart Study). Results In the NHS, Hp2-2 genotype (39% frequency) was strongly related to CHD risk only among individuals with elevated HbA(1c) (>= 6.5%), an association that was similar in the ICARE trial and the Strong Heart Study. In a pooled analysis, participants with both the Hp2-2 genotype and elevated HbA(1c) had a relative risk of 7.90 (95% confidence Interval: 4.43 to 14.10) for CHD compared with participants with both an Hp1 allele and HbA(1c) <6.5% (p for interaction = 0.004), whereas the Hp2-2 genotype with HbA(1c) <6.5% was not associated with risk (relative risk: 1.34 [95% confidence interval: 0.73 to 2.46]). Conclusions Hp genotype was a significant predictor of CHD among individuals with elevated HbA(1c). (J Am Coll Cardiol 2013; 61: 728-37) c 2013 by the American College of Cardiology Foundation

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