Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is associated with increased leptin levels in women with type-2 diabetes mellitus

Horm Res. 2002;58(3):143-9. doi: 10.1159/000064490.

Abstract

Objective: To analyze the relationship between the peroxisome proliferator-activated receptor-gamma (PPARgamma2) Pro12Ala variant and type-2 diabetes mellitus and its correlation with some cytokine determinants of insulin resistance such as tumor necrosis factor (TNF)-alpha and leptin.

Methods: The PPARgamma2 Pro12Ala genetic polymorphism was studied in 167 type-2 diabetic patients and 63 healthy controls. Serum leptin and plasma-soluble TNF-R2 were measured.

Results: Women carriers of the Pro12Ala mutation exhibited higher leptin levels than women non-carriers (median 31.4 vs. 17.5 ng/ml; p < 0.005). sTNF-R2 levels did not show differences between the two genotypes. Analysis by the multiple linear regression model of leptin-body mass index controlled by the PPARgamma2 genotype showed that leptin levels were determined by the Pro12Ala mutation in type-2 diabetic women but not in men.

Conclusions: PPARgamma2 seems to be implicated in leptin homeostasis in type-2 diabetic women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alanine*
  • Alleles
  • Antigens, CD / blood
  • Body Mass Index
  • Cytokines / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Heterozygote
  • Humans
  • Leptin / blood*
  • Linear Models
  • Male
  • Middle Aged
  • Mutation*
  • Obesity / blood
  • Proline*
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Leptin
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor, Type II
  • Sex Characteristics
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*

Substances

  • Antigens, CD
  • Cytokines
  • LEPR protein, human
  • Leptin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Leptin
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • Transcription Factors
  • Proline
  • Alanine