Haptoglobin genotype and cerebrovascular disease incidence in type 1 diabetes

Diab Vasc Dis Res. 2014 Sep;11(5):335-42. doi: 10.1177/1479164114539713. Epub 2014 Jul 3.

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).

Conclusion: 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.

Keywords: Type 1 diabetes; coronary artery disease; haptoglobin genotype; hypertension; stroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetic Angiopathies / diagnosis
  • Diabetic Angiopathies / epidemiology*
  • Diabetic Angiopathies / genetics
  • Diabetic Angiopathies / immunology
  • Female
  • Gene Frequency
  • Genotype
  • Haptoglobins / genetics*
  • Humans
  • Hypertension / epidemiology
  • Incidence
  • Male
  • Pennsylvania / epidemiology
  • Phenotype
  • Prognosis
  • Prospective Studies
  • Protective Factors
  • Risk Assessment
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / epidemiology*
  • Stroke / genetics
  • Stroke / immunology
  • Time Factors
  • Young Adult

Substances

  • HP protein, human
  • Haptoglobins