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 theICARE (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).
RCT Entities:
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 DiabeticPatients 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).
Authors: Andrew P Levy; Joanne E Levy; Shiri Kalet-Litman; Rachel Miller-Lotan; Nina S Levy; Roy Asaf; Julia Guetta; Chingwen Yang; K Raman Purushothaman; Valentin Fuster; Pedro R Moreno Journal: Arterioscler Thromb Vasc Biol Date: 2006-10-26 Impact factor: 8.311
Authors: Jennifer K Pai; Tobias Pischon; Jing Ma; JoAnn E Manson; Susan E Hankinson; Kaumudi Joshipura; Gary C Curhan; Nader Rifai; Carolyn C Cannuscio; Meir J Stampfer; Eric B Rimm Journal: N Engl J Med Date: 2004-12-16 Impact factor: 91.245
Authors: Leah E Cahill; Majken K Jensen; Stephanie E Chiuve; Hadar Shalom; Jennifer K Pai; Alan J Flint; Kenneth J Mukamal; Kathryn M Rexrode; Andrew P Levy; Eric B Rimm Journal: J Am Coll Cardiol Date: 2015-10-20 Impact factor: 24.094
Authors: Miriam Lipiski; Jeremy W Deuel; Jin Hyen Baek; Wolfgang R Engelsberger; Paul W Buehler; Dominik J Schaer Journal: Antioxid Redox Signal Date: 2013-03-28 Impact factor: 8.401
Authors: Leah E Cahill; Majken K Jensen; Daniel I Chasman; Aditi Hazra; Andrew P Levy; Eric B Rimm Journal: J Am Coll Cardiol Date: 2013-06-07 Impact factor: 24.094