Association of polymorphisms in the interleukin 6 receptor complex with obesity and hyperandrogenism

Obes Res. 2003 Aug;11(8):987-96. doi: 10.1038/oby.2003.136.

Abstract

Objective: Interleukin-6 (IL-6), is an inflammatory cytokine that may influence the pathogenesis of obesity and hyperandrogenism. IL-6 exerts its actions through a heterodimeric receptor consisting of two membrane-bound glycoproteins: an 80-kDa IL-6 binding unit (IL6R-alpha) and a 130-kDa IL-6 signal transducer (gp130). Genetic variability at these loci might contribute to explain the development of obesity and hyperandrogenism.

Research methods and procedures: We have evaluated the possible association of several polymorphisms in the IL6R-alpha and gp130 genes with obesity and/or hyperandrogenism in a case-control study involving 143 hyperandrogenic patients and 45 healthy women from Spain.

Results: A microsatellite CA-repeat polymorphism in the IL6R-alpha locus was associated with obesity. The frequency of the common 149-bp allele was markedly increased in obese women compared with controls when considering patients and controls as a whole (0.41 vs. 0.29, chi(2) = 17.085, p < 0.050). On the other hand, the uncommon Arg148 allele of the Gly148Arg polymorphism in the gp130 gene was more frequent in controls compared with hyperandrogenic patients (0.17 vs. 0.08, chi(2) = 5.605, p = 0.026). Controls carrying Arg148 alleles had lower 11-deoxycortisol and 17-hydroxyprogesterone concentrations, a lower response of androstenedione to 1-24 adrenocorticotropin, and an almost significant decrease in free testosterone levels, suggesting that Arg148 alleles in the gp130 gene have a protective effect against androgen excess and adrenal hyperactivity.

Discussion: Polymorphisms in the gp130 and IL6R-alpha loci influence hyperandrogenism and obesity, respectively. Our present results further suggest that proinflammatory genotypes are involved in the pathogenesis of these common metabolic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics*
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Cytokine Receptor gp130
  • DNA / chemistry
  • DNA / genetics
  • Female
  • Hormones / blood
  • Humans
  • Hyperandrogenism / blood
  • Hyperandrogenism / genetics*
  • Insulin / blood
  • Membrane Glycoproteins / genetics*
  • Microsatellite Repeats / genetics
  • Obesity / blood
  • Obesity / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Receptors, Interleukin-6 / genetics*

Substances

  • Antigens, CD
  • Blood Glucose
  • Hormones
  • IL6ST protein, human
  • Insulin
  • Membrane Glycoproteins
  • Receptors, Interleukin-6
  • interleukin-6 receptor alpha
  • Cytokine Receptor gp130
  • DNA