IL6R gene, plasma CRP, and diabetes risk in women

Abstract

Objective: Recent genome-wide association studies (GWAS) related common variants in the interleukin 6 receptor (IL6R) gene to plasma C-reactive protein (CRP) concentrations. Because IL6R variants were previously associated with IL-6 levels, we tested whether the associations with CRP were independent of IL-6 and the interactions between IL6R variants and CRP in relation to diabetes risk.

Research Design and Methods: Plasma CRP and IL-6 levels and ten IL6R polymorphisms were determined in a nested case-control study of 633 diabetic and 692 healthy Caucasian women.

Results: In both non-diabetic and diabetic women, IL6R polymorphisms were associated with plasma CRP levels, independent of IL-6 concentration. After adjustment of IL-6 levels, CRP concentrations in the genotype AA, AC, and CC of the GWAS polymorphism rs8192284 were 0.32, 0.26, and 0.24 pg/mL among non-diabetic women (P for trend=0.003; and FDR=0.01); and 0.63, 0.48, 0.43 pg/mL among diabetic women (P for trend<0.0001; and FDR=0.0001). Haplotypes inferred from polymorphisms within a linkage disequilibrium (LD) block including rs8192284 were also significantly associated with CRP levels (P=0.0002). In an exploratory analysis, rs8192284 showed significant interactions with CRP levels in relation to diabetes risk (P for interaction=0.026). The odds ratios across increasing quartiles of CRP were 2.19 [95% confidence interval (CI), 1.42−3.36], 2.03 (1.27−3.23), and 2.92 (1.77−4.82) in the carriers of allele-C; and were 2.21 (1.18−4.12), 3.77 (1.87−7.57), and 5.02 (2.4−10.5) in the non-carriers.

Conclusions: IL6R variants were significantly associated with plasma CRP, independent of IL-6 levels. IL6R variants may interact with CRP in predicting diabetes risk.