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

Sanderson, Saskia C.; Kumari, Meena; Brunner, Eric J.; Miller, Michelle A.; Rumley, Ann; Lowe, Gordon D.; Marmot, Michael G.; Humphries, Steve E.

doi:10.1016/j.atherosclerosis.2008.09.019

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Volume 204, Issue 2 , Pages 459-464, June 2009

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

Saskia C. Sanderson
- Department of Epidemiology and Public Health (Whitehall II), 1-19 Torrington Place, University College London, London WC1E 6BT, UK
- Centre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, UK
- Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, 31 Center Drive, Building 31, Room B1B37C, Bethesda, MD 20892, United States
Meena Kumari
- Department of Epidemiology and Public Health (Whitehall II), 1-19 Torrington Place, University College London, London WC1E 6BT, UK
- Corresponding author. Tel.: +44 20 7679 8825; fax: +44 20 7813 0242.
Eric J. Brunner
- Department of Epidemiology and Public Health (Whitehall II), 1-19 Torrington Place, University College London, London WC1E 6BT, UK
Michelle A. Miller
- Clinical Sciences Research Institute, UHCW Campus, Warwick Medical School, Clifford Bridge Road, Coventry, CV2 2DX, UK
Ann Rumley
- Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, Scotland, G31 2ER, UK
Gordon D. Lowe
- Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, Scotland, G31 2ER, UK
Michael G. Marmot
- Department of Epidemiology and Public Health (Whitehall II), 1-19 Torrington Place, University College London, London WC1E 6BT, UK
Steve E. Humphries
- Centre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, UK

Received 8 May 2008; received in revised form 29 August 2008; accepted 15 September 2008. published online 19 November 2008.

Abstract

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.

Keywords: Epidemiology, Genes, Genetics, Inflammation, Interleukins