Interleukin-6 genetic variability and adiposity: associations in two prospective cohorts and systematic review in 26,944 individuals

J Clin Endocrinol Metab. 2007 Sep;92(9):3618-25. doi: 10.1210/jc.2007-0877. Epub 2007 Jul 10.


Context: IL-6 (IL6) is an immune-modulating cytokine associated with obesity in humans.

Objective: Our objective was to assess the associations between the genetic variability of IL6 gene and adiposity and long-term changes.

Design and subjects: We determined the linkage disequilibrium-tagging single-nucleotide polymorphisms of IL6 gene in 2255 healthy women and 980 healthy men from two prospective cohorts. We also conducted a metaanalysis on the associations between polymorphism -174G>C (rs1800795) and adiposity.

Results: IL6 haplotype 222211 (possessing rs2069827, rs1800797, rs1800795, rs1554606, rs2069861, and rs1818879; 1 codes the common and 2 codes the minor alleles) was consistently and significantly associated with greater waist circumference (P = 0.009 in men; P = 0.0003 in women) and baseline body mass index (BMI) (P = 0.01 in men; P = 0.046 in women) compared with the most common haplotype 111112. Haplotype 222211 was also associated with significantly higher early-adulthood BMI in women (P = 0.007). The haplotype-associated difference in BMI persisted significantly during the follow-up. A 5' promoter polymorphism, rs2069827, was consistently associated with significantly higher early-adulthood BMI, baseline BMI, and waist circumference in men (carriers vs. noncarriers, P = 0.01, 0.007, and 0.008) and women (P = 0.01, 0.10, and 0.0016). The data from this study and a metaanalysis of 26,944 individuals did not support substantial relations between the best-studied polymorphism, -174G>C, and adiposity.

Conclusions: Our data from two independent cohorts indicate that the variability of the IL6 gene is significantly associated with adiposity. Such associations are less likely to be caused by polymorphism -174G>C.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adiposity / genetics*
  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Genetic Variation*
  • Health Personnel
  • Humans
  • Interleukin-6 / genetics*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Prospective Studies


  • Interleukin-6