Interleukin-1 polymorphisms associated with central obesity and metabolic syndrome in a coronary heart disease population
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Interleukin-1 (IL-1) is a pro-inflammatory cytokine with demonstrated effects on fat mass and metabolism, and on insulin sensitivity. In order to investigate whether single nucleotide polymorphisms (SNPs) in the IL-1 gene family are associated with central obesity and metabolic syndrome, two IL-1 SNPs (IL-1alpha C-889T (rs1800587) and IL-1beta +3954 (rs1143634)) were studied in 556 patients from Western Australia presenting with coronary heart disease (CHD). Patients who were TT homozygous at either SNP exhibited significantly larger waist circumference compared with major allele homozygotes. Subjects with two copies of the IL-1alpha:IL-1beta T:T haplotype had significantly greater waist circumference compared with other haplotypes. A significant interaction between the IL-1beta SNP and BMI level on waist circumference was found. Following stratification by median BMI, TT carriers for IL-1beta with above-median BMI had significantly greater waist circumference compared to baseline carriers whereas those with below-median BMI did not. Furthermore, when stratifying by median fibrinogen level, TT carriers for both SNPs in the above-median fibrinogen group had significantly greater waist circumference compared with major allele homozygotes, whereas those in the below-median group did not. Metabolic syndrome tended to be increased in IL-1beta TT homozygotes. These study results suggest that IL-1 gene polymorphisms in CHD patients may be involved in increased central obesity, the genetic influences being more evident among patients with higher levels of obesity and/or inflammatory markers.
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