title: Haptoglobin genotype and cerebrovascular disease incidence in type 1 diabetes.
abstract: OBJECTIVE
  We prospectively evaluated the haptoglobin (Hp)-stroke association in type 1 diabetes and hypothesized that despite increasing the risk of coronary artery disease, the presence of the Hp 2 allele would be associated with a lower incidence of stroke.
  
  
  METHODS
  Participants from the Epidemiology of Diabetes Complications study without prevalent stroke and Hp available were evaluated (n = 607; mean age 27.6 years and duration 19.3 years).
  
  
  RESULTS
  During 22 years of follow-up, stroke incidence did not differ by Hp genotype (p = 0.49). Restricting analyses to those diagnosed with diabetes ≥1965 (13% mortality vs 40% in the <1965 cohort) to diminish potential survival bias, the adjusted hazard ratio (HR) for Hp 1-1 was 3.08 (95% confidence interval (CI) = 0.81-11.77, p = 0.10). Further stratifying by hypertension prevalence, an increased stroke incidence was observed with Hp 1-1 only in those with hypertension (HR = 7.03, 95% CI = 1.42-34.89, p = 0.02).
  
  
  CONCLUSIONS
  Despite the protective effect against vascular diabetes complications, a borderline increased risk of stroke was observed with Hp 1-1 in type 1 diabetes. This mixed Hp effect on cardiovascular risk by outcome studied merits further investigation and cautions against the universal application of preventive therapies across all Hp genotypes.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA costacout@edc.pitt.edu.
authors.forename: Tina
authors.initials: T
authors.lastname: Costacou
authors.affiliation: Department of Dermatology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Secrest
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D008297:Male; D010414:Pennsylvania / Q000453:epidemiology; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D055815:Young Adult
chemical_list: C485359:HP protein, human; D006242:Haptoglobins
keywords: Type 1 diabetes; coronary artery disease; haptoglobin genotype; hypertension; stroke