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

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• 作者：Leah E. Cahill ; PhD^? ; ^{lcahill@hsph.harvard.edu} ; Andrew P. Levy ; MD ; PhD^&dagger ; ; Stephanie E. Chiuve ; ScD^? ; ^&Dagger ; ; Majken K. Jensen ; PhD^? ; Hong Wang ; MD^§ ; ; Nawar M. Shara ; PhD^§ ; ; Shany Blum ; MD ; PhD^&dagger ; ; Barbara V. Howard ; MD^§ ; ; Jennifer K. Pai ; ScD^¡Î ; ^¶ ; ; Kenneth J. Mukamal ; MD ; MPH^# ; Kathryn M. Rexrode ; MD ; MPH^&Dagger ; ; ^¡Î ; Eric B. Rimm ; ScD^? ; ^¡Î ; ^¶ ;
• 关键词：acute myocardial infarction ; coronary disease ; epidemiology ; genetic association ; genotype ; glycoproteins
• 刊名：Journal of the American College of Cardiology
• 出版年：2013
• 出版时间：19 February, 2013
• 年：2013
• 卷：61
• 期：7
• 页码：728-737
• 全文大小：1082 K

文摘

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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 (¡Ý6.5 % ), 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.