Interleukin-6 (IL-6)-572C→G promoter polymorphism is associated with type 2 diabetes risk in Koreans

Increased levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with type 2 diabetes (T2DM). We investigated the association of IL-6 gene polymorphisms with T2DM and circulating levels of IL-6 in Koreans. A total of 1477 subjects with normal glucose tolerance and 476 T2DM patients were included. We examined IL-6 -174G -> C, -572C -> G, -597G -> A and -1363G -> T promoter region polymorphisms. The main outcome measures were the odds ratio (OR) on T2DM risk and serum concentrations of IL-6 and high-sensitivity C-reactive protein (hs-CRP). Homozygosity for the rare G allele IL-6 -572C -> G was associated with a higher risk of T2DM [OR 1.69 (95%CI 1.11-2.58), P = 0.015]. Serum IL-6 concentrations were associated with the IL-6 -572C -> G genotype in control subjects (G/G: 2.33 +/- 0.41: C/G: 1.53 +/- 0.09: C/C: 1.72 +/- 0.08 ng/l, P = 0.023). Also in the control group, subjects homozygous for the rare G allele showed significantly higher concentrations of hs-CRP than C/C and C/G carriers (G/G: 13.6 +/- 2.9: C/G: 9.2 +/- 0.6: C/C: 7.8 +/- 0.4 mg/l, P = 0.003). The C-allele at the IL-6 -174 SNP was very rare (< 0.01) and -597G -> A and -1363G -> T were monomorphic in this population. Our data demonstrate that the IL-6 -572G/G genotype is associated with higher serum IL-6 and hs-CRP concentrations and with increased risk for T2DM.