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

被引：74

作者：

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, Shany ^{[2
]}

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
]}

机构：

[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

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2013年 / 61卷 / 07期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

acute myocardial infarction; coronary disease; epidemiology; genetic association; genotype; glycoproteins; DIABETES-MELLITUS; GLUCOSE CONTROL; POLYMORPHISM; PHENOTYPE; METAANALYSIS; OUTCOMES; IRON; MEN;

D O I：

10.1016/j.jacc.2012.09.063

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

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

引用

页码：728 / 737

页数：10

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