Pro198Leu Polymorphism in the Glutathione Peroxidase 1 Gene Contributes to Diabetic Peripheral Neuropathy in Type 2 Diabetes Patients

Neuromolecular Med. 2017 Mar;19(1):147-153. doi: 10.1007/s12017-016-8438-2. Epub 2016 Sep 3.

Abstract

Glutathione peroxidase 1 (Gpx1) is an endogenous antioxidant enzyme. The T allele of the Pro198Leu polymorphism in the Gpx1 (rs1050450, 198C > T) gene is associated with reduced enzyme activity. The aim of this study was to evaluate the association between Pro198Leu polymorphism and risk of diabetic peripheral neuropathy (DPN). We examined 1244 T2DM patients and 730 healthy controls. In the patient group, 33 % had diabetic peripheral neuropathy. All subjects were genotyped for the Gpx1 Pro198Leu polymorphism by polymerase chain reaction and restriction analysis. A significant increase in the T allele and TT genotype frequencies was observed in DPN patients compared to those without DPN (OR 1.55, 95 % CI 1.30-1.85 and 1.89, 95 % CI 1.30-2.74, respectively). The association remained significant after correction for age, disease duration, HbA1c and BMI. When distribution of T allele was compared between DPN+ and DPN- subgroups and controls, OR was 1.54 for DPN+ and 1.00 for DPN- patients. In conclusion, our findings suggest that Gpx1 Pro198Leu genotypes are significantly associated with the risk of diabetic peripheral neuropathy in patients with T2DM. The study provides new clinically relevant information regarding genetic determinants of susceptibility to diabetic neuropathy.

Keywords: Gpx1; Peripheral neuropathy; Pro198Leu polymorphism; Risk allele; Type 2 diabetes.

MeSH terms

  • Age of Onset
  • Aged
  • Alleles
  • Cardiovascular Diseases / epidemiology
  • Case-Control Studies
  • Comorbidity
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Neuropathies / enzymology
  • Diabetic Neuropathies / epidemiology
  • Diabetic Neuropathies / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Glutathione Peroxidase / genetics*
  • Glutathione Peroxidase / physiology
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hyperlipidemias / epidemiology
  • Male
  • Middle Aged
  • Poland / epidemiology
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*

Substances

  • Glycated Hemoglobin A
  • glutathione peroxidase GPX1
  • Glutathione Peroxidase