Contribution Of The Functional 5-Httlpr Variant Of The Slc6a4 Gene To Obesity Risk In Male Adults.

SOOKOIAN S; FERNANDEZ GIANOTTI T; GEMMA C; BURGUEÑO A; PIROLA CJ,

Obesity (Silver Spring)

Nature Publishing Group

Lugar: London, United Kindom; Año: 2008 vol. 16 p. 488 - 491

1930-7381

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.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 crosssectional, population-based study.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 crosssectional, 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.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 ¡À 0.3 years, age-adjusted BMI values (expressed as mean ¡À s.e.) for each genotype showed statistically significant differences across genotypic groups (LL: 25.4 ¡À 0.2, LS: 26.0 ¡À 0.1 and SS: 26.7 ¡À 0.2, P < 0.0002). In addition, association tests showed that the 5-HTTLPR-genotype distribution was significantly different between 692 lean (BMI ¡Ü 25 kg/m2) and 637 obese (BMI¡Ý 27 kg/m2) individuals. We found a 1.36 odds ratio (OR) (95% CI 1.01¨C1.85) for obesity in SS carriers in comparison with LL carriers, P = 0.026.We observed that among 1,329 unrelated subjects, aged 34.6 ¡À 0.3 years, age-adjusted BMI values (expressed as mean ¡À s.e.) for each genotype showed statistically significant differences across genotypic groups (LL: 25.4 ¡À 0.2, LS: 26.0 ¡À 0.1 and SS: 26.7 ¡À 0.2, P < 0.0002). In addition, association tests showed that the 5-HTTLPR-genotype distribution was significantly different between 692 lean (BMI ¡Ü 25 kg/m2) and 637 obese (BMI¡Ý 27 kg/m2) individuals. We found a 1.36 odds ratio (OR) (95% CI 1.01¨C1.85) 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.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.