Association of Interleukin-1 gene polymorphisms with central obesity and metabolic syndrome in a coronary heart disease population

Date

2008

Authors

Carter, K.
Hung, J.
Powell, B.
Wiltshire, S.
Foo, B.
Leow, Y.
McQuillan, B.
Jennens, M.
McCaskie, P.
Thompson, P.

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Human Genetics, 2008; 124(3):199-206

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Kim W. Carter, Joseph Hung, Brenda L. Powell, Steven Wiltshire, Brendan T. X. Foo, Yuen C. Leow, Brendan M. McQuillan, Michelle Jennens, Pamela A. McCaskie, Peter L. Thompson, John P. Beilby, Lyle J. Palmer

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Abstract

The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) in the Interleukin-1 (IL-1) gene family are associated with central obesity and metabolic syndrome in a coronary heart disease population. The IL-1α C-889T (rs1800587) and IL-1β +3954 (rs1143634) SNPs were studied in a Western Australian coronary heart disease (CHD) population (N = 556). Subjects who were TT homozygous at either SNP had larger waist circumference (IL-1α: 1.8 cm greater, P = 0.04; IL-1β: 4 cm greater, P = 0.0004) compared with major allele homozygotes. Individuals with two copies of the IL-1α:IL-1β T:T haplotype had greater waist circumference (4.7 cm greater, P = 0.0001) compared to other haplotypes. There was a significant interaction between the IL-1β SNP and BMI level on waist circumference (P = 0.01). When the cohort was stratified by median BMI, TT carriers for IL-1β with above median BMI had greater waist circumference (6.1 cm greater, P = 0.007) compared to baseline carriers, whilst no significant association was seen in the below median group. Similarly, when the cohort was stratified by median fibrinogen level (IL-1α interaction P = 0.01; IL-1β interaction P = 0.04), TT carriers for both SNPs in the above median fibrinogen group had greater waist circumference (IL-1α 2.7 cm greater, P = 0.007; IL-1β 3.3 cm greater, P = 0.003) compared with major allele homozygotes. This association was not seen in the below median group. Also, we found a trend of increased metabolic syndrome for IL-1β TT homozygotes (P = 0.07). In conclusion, our findings suggest that in a CHD population IL-1 gene polymorphisms may be involved in increased central obesity, and the genetic influences are more evident among patients who have a higher level of obesity or inflammatory markers.

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© Springer-Verlag 2008

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