Contribution of the functional 5-HTTLPR variant of the SLC6A4 gene to obesity risk in male adults

Abstract

Background:A polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) gene SLC6A4 shows functionally important 44-bp insertion/deletion alleles: long (L) and short (S). We have previously found that the S allele is a genetic risk factor for obesity in adolescents.Objective: The aim of this study was to evaluate whether the S/L variant of the SLC6A4 gene is associated with BMI as a continuous trait and also with obesity in a large sample of adult men of European ancestry included in a cross-sectional, population-based study.Methods and Procedures:The study group was composed of individuals who were randomly recruited from a factory in the Buenos Aires metropolitan area and who underwent an annual health examination.Results:We observed that among 1,329 unrelated subjects, aged 34.6 0.3 years, age-adjusted BMI values (expressed as mean s.e.) for each genotype showed statistically significant differences across genotypic groups (LL: 25.4 0.2, LS: 26.0 0.1 and SS: 26.7 0.2, P 0.0002). In addition, association tests showed that the 5-HTTLPR-genotype distribution was significantly different between 692 lean (BMI 25 kg/m2) and 637 obese (BMI 27 kg/m2) individuals. We found a 1.36 odds ratio (OR) (95% CI 1.01-1.85) for obesity in SS carriers in comparison with LL carriers, P 0.026.Discussion:In conclusion, our findings indicate that 5-HTTLPR polymorphism may be linked with BMI and also with obesity and/or overweight in adult male population, reinforcing the role of the serotonin transporter as a risk factor for the obesity phenotype and suggesting potential new avenues for its pharmacological treatment. © 2008 The Obesity Society.