Genetic and environmental nature of the insulin resistance syndrome in Indo-Mauritian subjects with premature coronary heart disease: contribution orbeta 3-adrenoreceptor gene polymorphism and beta blockers on triglyceride and HDL concentrations

Aims/hypothesis. Insulin resistance syndrome is an important risk factor fo r developing premature coronary heart disease. It is a complex syndrome whi ch could arise from the interaction of several genes modulated by environme ntal factors. The Trp64Arg polymorphism in the beta3-adrenoreceptor gene ha s been found to be associated with insulin resistance, obesity or with earl ier onset of Type II (non-insulin-dependent) diabetes mellitus in different populations. We aimed to study whether features of the insulin resistance syndrome are associated with this polymorphism in Indo-Mauritian patients w ith premature coronary heart disease. Methods. We carried out a case control study using PCR-RFLP techniques, of consecutive Indo-Mauritian patients (n = 338) with premature coronary heart disease (onset below age of 60 years) and unrelated control subjects (n = 148) of the same ethnicity. Results. In Indo-Mauritian patients with premature coronary heart disease w ho were not treated by beta blockers, triglyceride concentrations were lowe r (me-dian: 1.44 vs 1.93 mmol/l, p < 0.008) and HDL cholesterol concentrati ons higher (mean: 0.98 vs 0.85 mmol/l, p < 0.015) in those carrying the wil d type of the beta3-adrenoreceptor gene than in those carrying the Trp64Arg variant. The latter genotype specific effect on HDL was inverse in patient s treated with beta blockers. Conclusion/interpretation. The beta3-adrenoreceptor gene variant seems to m odulate the effects of beta blockers on triglyceride and HDL cholesterol co ncentrations in this group of Indo-Mauritian population. Dyslipidaemia, a k ey component of the metabolic syndrome has a heterogeneous nature in Indo-M auritian subjects. This potent risk factor for early-onset coronary heart d isease is influenced by the interaction between genetic and environmental e ffects.