A polymorphism at the IL6ST (gp130) locus is associated with traits of the metabolic syndrome

Obesity (Silver Spring). 2008 Jan;16(1):205-10. doi: 10.1038/oby.2007.28.


The interleukin 6 signal transducer (IL6ST, also known as gp130) is a ubiquitously expressed intermediate of the interleukin-6 signaling pathway. We investigated whether genetic variability at the IL6ST locus is involved in the modulation of metabolic traits and the etiology of the metabolic syndrome (MS). Four haplotype-tagging single nucleotide polymorphisms were typed in two populations of non-diabetic subjects, one from Northern Italy (Padua (PD), n = 630), the other from Southern Italy (San Giovanni Rotondo (SGR), n = 553). In the PD population, a nominally significant association was observed between fasting glucose and rs715180 (P = 0.02), rs3729960 (P = 0.02), and rs10940495 (P = 0.05), between homeostasis model assessment index (HOMA(IR)) and rs715180 (P = 0.04), and between triglycerides and rs3729960 (P = 0.03). In the SGR population, high-density lipoprotein (HDL) levels were associated with rs715180 (P = 0.01), systolic blood pressure and waist circumference with rs3729960 (P = 0.005 and 0.02, respectively). The frequency of rs715180 minor allele carriers progressively decreased from individuals with no MS components to those with three or more components (P for trend = 0.006 in the two populations combined). Compared to major allele homozygotes, minor allele carriers had 40% lower odds of having at least one MS component (Odds ratio = 0.6, 95% confidence interval 0.4-0.8, P = 0.005). These findings point to IL6ST variants as possible determinants of impaired glucose metabolism and other abnormalities of MS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cytokine Receptor gp130 / genetics*
  • Female
  • Gene Frequency / genetics
  • Genetics, Population
  • Genotype
  • Glucose / metabolism
  • Haplotypes / genetics
  • Humans
  • Italy
  • Linkage Disequilibrium / genetics
  • Male
  • Metabolic Syndrome / ethnology
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*


  • Cytokine Receptor gp130
  • Glucose