title: Haptoglobin genotype is a consistent marker of coronary heart disease risk among individuals with elevated glycosylated hemoglobin.
abstract: OBJECTIVE
  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).
authors: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts. lcahill@hsph.harvard.edu
authors: Leah E
authors: LE
authors: Cahill
authors: Andrew P
authors: AP
authors: Levy
authors: Stephanie E
authors: SE
authors: Chiuve
authors: Majken K
authors: MK
authors: Jensen
authors: Hong
authors: H
authors: Wang
authors: Nawar M
authors: NM
authors: Shara
authors: Shany
authors: S
authors: Blum
authors: Barbara V
authors: BV
authors: Howard
authors: Jennifer K
authors: JK
authors: Pai
authors: Kenneth J
authors: KJ
authors: Mukamal
authors: Kathryn M
authors: KM
authors: Rexrode
authors: Eric B
authors: EB
authors: Rimm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000235:genetics* / Q000378:metabolism; D006031:Glycosylation; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D006242:Haptoglobins; C485359:HP protein, human; C517652:hemoglobin A1c protein, human