Haptoglobin genotype is associated with increased endothelial dysfunction serum markers in type 1 diabetes

Eur J Clin Invest. 2015 Sep;45(9):932-9. doi: 10.1111/eci.12487. Epub 2015 Aug 6.

Abstract

Background: To evaluate the genotype-driven effect of haptoglobin (Hp) in patients with type 1 diabetes without clinical cardiovascular (CV) disease, considering endothelial dysfunction (ED) and arterial stiffness (AS).

Material and methods: About 137 patients with type 1 diabetes (duration ≥ 5 years) and 68 age- and sex-matched controls were evaluated for the following: (i) smoking, alcohol intake, BMI, blood pressure, fasting plasma glucose, HbA1c and lipid profile; (ii) microvascular complications; (iii) serum markers of ED (ICAM-1, VCAM-1 and E-selectin); (iv) AS, assessed as aortic pulse wave velocity (aPWV); and (v) Hp genotype.

Results: The prevalence of the 1/1, 2/1 and 2/2 Hp genotypes was 28.5%, 46.7% and 24.8% in patients with type 1 diabetes and 20.9%, 38.8% and 40.3% in controls, respectively. No differences were found in classical CV risk factors between patients homozygous for allele 2 and the remaining genotypes, both in patients with type 1 diabetes and controls. Patients with type 1 diabetes carrying the Hp2/2 genotype had higher concentrations of ICAM-1 (65.1 (56.7-76.0) ng/mL vs. 59.0 (51.7-69.3) ng/mL; P = 0.033) and sVCAM-1 (1133.1 (884.6-1458.6) ng/mL vs. 956.4 (738.5-1206.1) ng/mL; P = 0.040) than those without it. The Hp2/2 genotype remained independently associated with ED after adjusting for CV risk factors (P = 0.038). No significant differences were found for aPWV between Hp genotypes.

Conclusions: Endothelial dysfunction may be influenced by Hp2/2 genotype in patients with type 1 diabetes with independence of classical CV risk factors.

Keywords: Arterial stiffness; endothelial dysfunction; haptoglobin genotype; type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / physiopathology*
  • E-Selectin / metabolism
  • Endothelium, Vascular / physiopathology*
  • Female
  • Gene Expression Regulation
  • Genotype
  • Haptoglobins / genetics*
  • Homozygote
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Middle Aged
  • Pulse Wave Analysis
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vascular Stiffness / genetics*
  • Young Adult

Substances

  • Biomarkers
  • E-Selectin
  • Haptoglobins
  • SELE protein, human
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1