Gender specific associations of the Trp64Arg mutation in the beta(3)-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation

Objective. To investigate the association between the Trp64Arg beta (3)-adr energic receptor (ADRB3) mutation and obesity-related phenotypes in a Medit erranean Spanish population considering the effect of other genetic and env ironmental factors. Design and subject. Cross-sectional study in 1063 (476 men and 587 women) r andomly selected from this population (aged: 18-68 years). Measurements. Anthropometric (weight, height and waist-to-hip ratio), blood pressure, biochemical (lipids, fasting glucose, and uric acid), life-style variables, and the Trp64Arg, HindIII-Lipoprotein lipase (LPL) and apolipop rotein E polymorphism. Results. Frequency of the Arg64 allele was low (0.051; 95% CI: 0.042-0.060) . We found gender-specific associations between the Trp64Arg mutation and o besity related phenotypes. In men, carriers of the Arg64 variant had higher body mass index (BMI) (27.63 +/-3.81 vs. 26.34 +/-3.57 kg m(-2) P=0.049) a nd total cholesterol (5.85 +/-1.45 vs. 5.28 +/-1.06 mmol L-1; P=0.011) comp ared with wild-type individuals. Logistic regression analysis, revealed tha t the risk of overweight was two times higher in mate carriers of the Arg64 allele. In women, the Arg64 variant was only associated with higher fastin g glucose (P=0.031). These genotype effects persisted after adjustment for age, genetic and life-style variables, For the LPL polymorphism, the H-/H- genotype was associated with lower BMI and with lower risk of overweight (O R: 0.49, 95% CI: 0.30-0.81) in both men and women. However, after adjustmen t for covariates, these associations only remained statistically significan t (P<0.02) in women. Moreover, in women, a statistically significant intera ction (P=0.026) between the LPL and the ADRB3 gene loci in determining BMI was found. Thus, the Arg64 allele was associated with a higher BMI only in H+/H+ women. Conclusions. The Trp64Arg mutation was associated with BMI and lipids in me n. In women, an additional gone-gene interaction with the LPL-HindIII polym orphism may explain the results.