Association of endothelial lipase Thr111Ile polymorphism with lipid metabolism and microvascular complications in type 2 diabetic patients

Diabetes Metab. 2011 Feb;37(1):64-71. doi: 10.1016/j.diabet.2010.07.010. Epub 2010 Dec 9.

Abstract

Aim: Endothelial lipase (EL) is a key enzyme in lipid metabolism, and a polymorphism in the EL gene may be a candidate for modulating lipid parameters in type 2 diabetic (T2D) patients.

Methods: In 396 T2D patients (age: 59.5 ± 10.7 years; BMI: 28.9 ± 5.3 kg/m(2); HbA(1c): 8.2 ± 1.9%), the c.584C>T polymorphism (rs2000813, p.Thr111Ile) was studied in 225 men (frequency of c.584T: 0.351) and 171 women (frequency of c.584T: 0.304). Patients' metabolic parameters, and macrovascular and microvascular complications, were assessed at baseline and at follow-up (mean: 4.2 years).

Results: Patients who were homozygous for the minor allele displayed modestly decreased low-density lipoprotein (LDL) cholesterol and raised apolipoprotein B at baseline, and raised systolic blood pressure and high-density lipoprotein (HDL) cholesterol on follow-up. Homozygosity for the minor allele was significantly associated with frequency of retinopathy (P=0.025), with TT homozygous patients more likely to have diabetic retinopathy (OR: 3.505; 95% CI: 1.491-8.239) both initially and at follow-up.

Conclusion: The c.584C>T EL polymorphism is associated with a higher risk of diabetic retinopathy that could be linked to modifications in HDL-cholesterol metabolism and blood pressure levels.

MeSH terms

  • Aged
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes Mellitus, Type 2* / metabolism
  • Diabetic Angiopathies* / epidemiology
  • Diabetic Angiopathies* / genetics
  • Diabetic Angiopathies* / metabolism
  • Diabetic Retinopathy* / epidemiology
  • Diabetic Retinopathy* / genetics
  • Diabetic Retinopathy* / metabolism
  • Endothelium, Vascular / enzymology
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease / epidemiology
  • Genotype
  • Homozygote
  • Humans
  • Lipase / genetics*
  • Lipase / metabolism*
  • Lipid Metabolism / genetics
  • Longitudinal Studies
  • Male
  • Microcirculation / physiology
  • Middle Aged
  • Polymorphism, Genetic
  • Risk Factors

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • LIPG protein, human
  • Lipase