Genetic and environmental nature of the insulin resistance syndrome in Indo-Mauritian subjects with premature coronary heart disease: contribution of beta3-adrenoreceptor gene polymorphism and beta blockers on triglyceride and HDL concentrations.
OBJECTIVE
Insulin resistance syndrome is an important risk factor for developing premature coronary heart disease. It is a complex syndrome which could arise from the interaction of several genes modulated by environmental factors. The Trp64Arg polymorphism in the beta3-adrenoreceptor gene has been found to be associated with insulin resistance, obesity or with earlier 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 with 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 who were not treated by beta blockers, triglyceride concentrations were lower (median: 1.44 vs 1.93 mmol/l, p < 0.008) and HDL cholesterol concentrations higher (mean: 0.98 vs 0.85 mmol/l, p < 0.015) in those carrying the wild type of the beta3-adrenoreceptor gene than in those carrying the Trp64Arg variant. The latter genotype specific effect on HDL was inverse in patients treated with beta blockers.


CONCLUSIONS
The beta3-adrenoreceptor gene variant seems to modulate the effects of beta blockers on triglyceride and HDL cholesterol concentrations in this group of Indo-Mauritian population. Dyslipidaemia, a key component of the metabolic syndrome has a heterogeneous nature in Indo-Mauritian subjects. This potent risk factor for early-onset coronary heart disease is influenced by the interaction between genetic and environmental effects.
Manraj
M
M
SSR Centre for Medical Studies and Research, University of Mauritius, Moka.
Francke
S
S
Hébé
A
A
Ramjuttun
U S
US
Froguel
P
P
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000419:Albuminuria / Q000150:complications; D001824:Body Constitution; D015992:Body Mass Index; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000150:complications / Q000235:genetics*; D004777:Environment; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D007333:Insulin Resistance / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D008436:Mauritius; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D012307:Risk Factors; D013577:Syndrome; D014280:Triglycerides / Q000097:blood
D000319:Adrenergic beta-Antagonists; D008076:Cholesterol, HDL; D008055:Lipids; D022702:Receptors, Adrenergic, beta-3; D014280:Triglycerides