A common interleukin 18 haplotype is associated with higher body mass index in subjects with diabetes and coronary heart disease

Abstract The pleiotropic proinflammatory cytokine, interleukin 18, plays a role in innate immunity and, based on mouse models, influences obesity. We investigated variation within the IL18 gene and its effect on markers of the metabolic syndrome. A tagging single nucleotide polymorphism set of 5 SNPs for the gene encoding interleukin 18 was selected and genotype was determined in 3 separate studies. In 2775 healthy middle-aged men, 6 common haplotypes were seen, but none was associated with body mass index (BMI). In 439 patients who underwent coronary artery bypass graft surgery, Hap2 (frequency, 22%) was present at a lower frequency than in healthy subjects and was associated with higher mean BMI compared with Hap1 ( P = .011). In 483 men with type 2 diabetes mellitus, Hap2 was again associated with a higher haplotypic mean BMI ( P = .002). Those homozygous for Hap2 had a BMI of 31.2 (1.3) kg/m 2 , mean (SE), compared with 28.3 (1.0) kg/m 2 in those not carrying a copy of Hap2. No single SNP could fully explain the effects seen. Therefore, variation within IL18 , previously shown to be associated with lower IL18 levels, is influencing measures of obesity both in men with type 2 diabetes mellitus and those with advanced coronary heart disease.