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.


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.
Sanderson
Saskia C
SC
Department of Epidemiology and Public Health (Whitehall II), 1-19 Torrington Place, University College London, London WC1E 6BT, UK.
Kumari
Meena
M
Brunner
Eric J
EJ
Miller
Michelle A
MA
Rumley
Ann
A
Lowe
Gordon D
GD
Marmot
Michael G
MG
Humphries
Steve E
SE
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004651:Employment; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D016014:Linear Models; D008131:London; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012923:Social Class; D012931:Social Environment; D013997:Time Factors
C508600:IL6 protein, human; D015850:Interleukin-6