Sookoian Silvia, Gianotti Tomas F, Gemma Carolina, Burgueño Adriana, Pirola Carlos J
Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research, A Lanari, University of Buenos Aires-CONICET, Buenos Aires, Argentina.
Obesity (Silver Spring). 2008 Feb;16(2):488-91. doi: 10.1038/oby.2007.64.
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.
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.
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.
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.
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.
血清素转运体（5-HTTLPR）基因SLC6A4启动子区域的一种多态性表现出功能上重要的44碱基对插入/缺失等位基因：长（L）和短（S）。我们之前发现S等位基因是青少年肥胖的遗传风险因素。
本研究旨在评估SLC6A4基因的S/L变体是否与体重指数（BMI）作为连续性状相关，以及在一项基于人群的横断面研究中纳入的大量欧洲血统成年男性样本中是否与肥胖相关。
研究组由从布宜诺斯艾利斯大都市区一家工厂随机招募并接受年度健康检查的个体组成。
我们观察到，在1329名年龄为34.6±0.3岁的无关受试者中，各基因型经年龄调整的BMI值（以均值±标准误表示）在基因型组间显示出统计学显著差异（LL：25.4±0.2，LS：26.0±0.1，SS：26.7±0.2，P<0.0002）。此外，关联测试表明，在692名瘦人（BMI≤25kg/m²）和637名肥胖者（BMI≥27kg/m²）个体之间，5-HTTLPR基因型分布存在显著差异。与LL携带者相比，我们发现SS携带者患肥胖症的优势比（OR）为1.36（9%CI 1.01-1.85），P=0.026。
总之，我们的研究结果表明，5-HTTLPR多态性可能与成年男性人群的BMI以及肥胖和/或超重有关，强化了血清素转运体作为肥胖表型风险因素的作用，并为其药物治疗提示了潜在的新途径。
