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The association of interleukin-18 genotype and serum levels with metabolic risk factors for cardiovascular disease

UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, PO BOX 115, Newlands, 7725 Cape Town, South Africa
¹ Diabetes and Endocrine Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa
² Biostatistics Unit, Medical Research Council of South Africa, Cape Town, South Africa
³ Department of Medicine, Umeå University, Umeå, Sweden

(Correspondence should be addressed to J H Goedecke Email: julia.goedecke{at}uct.ac.za)

Objective: Circulating levels of interleukin (IL)-18 are associated with the metabolic syndrome and risk for the development of cardiovascular disease (CVD). This study investigated the association between the circulating IL-18 levels and the –137 G/C polymorphism within the IL-18 gene with metabolic risk factors for CVD in normal-weight and obese black South African women.

Methods: Blood pressure (BP), body composition (dual-energy X-ray absorptiometer), visceral adiposity (computerized tomography), as well as fasting glucose, insulin, lipid profile, IL-18 levels, and IL-18 genotype were measured in 104 normal-weight (body mass index (BMI) 25 kg/m²) and 124 obese (BMI30 kg/m²) black South African women.

Results: Subjects with a GC genotype (23%) had a greater mean arterial pressure (MAP, 90.6±11.1 vs 85.5±10.3 mmHg, P<0.001) than the subjects with the GG genotype. Serum IL-18 levels were not associated with IL-18 genotype (P=0.985); however, they significantly correlated with percentage of body fat (r=0.25, P<0.001), visceral adiposity (r=0.32, P<0.001), MAP (r=0.22, P=0.001), HOMA-IR (r=0.33, P<0.001), fasting insulin (r=0.25, P<0.001), triglyceride (r=0.16, P<0.05), and high-density lipoprotein-cholesterol (r=–0.14, P<0.05) levels, after adjusting for age and body fatness.

Conclusions: We show for the first time that the GC genotype of the IL-18 –137 G/C polymorphism and the circulating IL-18 levels are independently associated with raised BP. Moreover, fasting IL-18 levels are associated with the other metabolic risk factors for CVD in normal-weight and obese black South African women.