Interleukin‐6 g.−174G>C Promoter Polymorphism Is Associated with Obesity in the EPIC‐Potsdam Study

Homozygosity for the interleukin‐6 (IL‐6) g.−174G>C promoter polymorphism has recently been associated with indices of overweight. Homozygous subjects were observed to have reduced energy expenditure, suggesting that lower IL‐6 gene transcription, caused by the IL‐6 g.−174G>C promoter polymorphism, may be associated with obesity. The aim of this study was to investigate the association of this polymorphism with long‐term weight gain. For 334 normal weight (20 < BMI ≤ 25 kg/m 2 ) and 334 obese (BMI > 30 kg/m 2 ) subjects matched by age and sex originating from the population‐based EPIC‐Potsdam Study, recalled weight change from age 25 to study enrollment was determined, the IL‐6 g.–174G>C promoter polymorphism was defined, and plasma concentrations of IL‐6 and C‐reactive protein were measured. The IL‐6 g.−174G>C promoter polymorphism was significantly associated with obesity (χ 2 = 7, 34, p = 0.026). Odds ratios for subjects with GC and CC genotypes for obesity were 1.19 (95% CI: 0.84 to 1.68; p = 0.323) and 1.91 (95% CI: 1.19 to 3.08; p = 0.007), respectively. Recalled weight change from age 25 years to study enrollment differed significantly according to genotype ( p = 0.044) and was most pronounced in subjects with the CC genotype, suggesting that the IL‐6 g.−174G>C promoter polymorphism is a susceptibility or modifying locus for common obesity and weight gain.