Haptoglobin genotype predicts development of coronary artery calcification in a prospective cohort of patients with type 1 diabetes

Abstract

BackgroundCoronary artery disease has been linked with genotypes for haptoglobin (Hp) which modulates extracorpuscular hemoglobin. We hypothesized that the Hp genotype would predict progression of coronary artery calcification (CAC), a marker of subclinical atherosclerosis.MethodsCAC was measured three times in six years among 436 subjects with type 1 diabetes and 526 control subjects participating in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. Hp typing was performed on plasma samples by polyacrylamide gel electrophoresis.ResultsThe Hp 2-2 genotype predicted development of significant CAC only in subjects with diabetes who were free of CAC at baseline (OR: 1.95, 95% CI: 1.07-3.56, p = 0.03), compared to those without the Hp 2-2 genotype, controlling for age, sex, blood pressure and HDL-cholesterol. Hp 2 appeared to have an allele-dose effect on development of CAC. Hp genotype did not predict CAC progression in individuals without diabetes.ConclusionsHp genotype may aid prediction of accelerated coronary atherosclerosis in subjects with type 1 diabetes.

Type 1 Diabetes Mellitus and Cardiovascular Disease

“…118 In the CACTI study group, the presence of the haptoglobin 2-2 genotype also doubled the risk of CAC in patients free from CAC at baseline, after adjustment for traditional CVD risk factors. 119 What is particularly exciting about these observations is the potential for preventing CVD with vitamin E in those with haptoglobin 2-2, as may occur in T2DM. [120][121][122][123] The relevance of these observations to patients with T1DM remains unexamined, and the haptoglobin 2-2 genotype has not been identified by genome-wide association studies.…”

Genotype-Dependent Impairment of Hemoglobin Clearance Increases Oxidative and Inflammatory Response in Human Diabetic Atherosclerosis

“…Hp2-2 genotype may also play a role in high-density lipoprotein function, reducing cholesterol efflux, as previously reported. 35 Finally, the clinical relevance of Hp2-2 genotype in other vascular territories different from peripheral vascular disease is supported by increases in coronary calcification, 39 myocardial infarction, 40 congestive heart failure, and cardiac death. 41 Our results extend these observations by suggesting a potential role for Hp2-2 genotype in the modulation of lower extremity atherosclerosis in the setting of DM.…”

Smoking and the correlation between birth weight and placental weight. Evidence of interaction with maternal haptoglobin phenotype

“…There is evidence of functional differences between polymers of Hp2-1 and polymers of Hp2 phenotypes [8]. This protein protects against hemoglobin peroxidation and its phenotypes have been linked to several diseases such as coronary artery disease, type 1 diabetes, Crohn's disease, inflammatory diseases, Parkinson, malaria, moreover it may be an indicator of neonatal jaundice, a predictor of nephropathy in type 2 diabetes and shows a protective role in the brain after intra-cerebral hemorrhage [9][10][11][12][13][14][15][16][17].…”