Contribution of the functional 5-HTTLPR variant of the SLC6A4 gene to obesity risk in male adults.
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
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 < or = 25 kg/m2) and 637 obese (BMI > or = 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.


CONCLUSIONS
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.
Sookoian
Silvia
S
Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research, A Lanari, University of Buenos Aires-CONICET, Buenos Aires, Argentina.
Gianotti
Tomas F
TF
Gemma
Carolina
C
Burgueño
Adriana
A
Pirola
Carlos J
CJ
D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins