Association between IL6 gene variants -174G>C and -572G>C and serum IL-6 levels: interactions with social position in the Whitehall II cohort.

Objective: To examine the impact of -174G>C and -572G>C variants in the promoter region of the IL6 gene, and their interactions with social position, on interleukin-6 (IL-6) levels in the Whitehall II cohort.

Methods And Results: SNPs were genotyped by TaqMan. IL-6 was measured by ELISA. Employment grade was assessed to indicate social position. ANOVAs were used to examine genotype-phenotype associations. 4165 white men and women provided data on IL-6 levels at two study time points, Phase 3 (1991-1993) and Phase 7 (2002-2004). Distributions were as expected for Hardy-Weinberg equilibrium. At Phase 3, overall IL-6 levels did not differ by either genotype, but -174C was associated with higher IL-6 levels within the lowest employment grades (p(interaction)=0.046). At Phase 7, IL-6 levels overall were 6% higher in -174C (p=0.002) and 9% lower in -572C (p=0.003) carriers. The lowering effect of -572C was not apparent in the lowest employment grades (p(interaction)=0.05).

Conclusions: IL-6 levels are determined in part by interaction between common functional IL6 gene variants and yet to be identified components of social position. These results highlight the importance of considering interactions between genes and social environments in future study designs.