Duarte S F P, Francischetti E A, Genelhu V A, Cabello P H, Pimentel M M G
Serviço de Genética Humana, Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
Genet Mol Res. 2007 Oct 5;6(4):1035-43.
Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. The adrenergic receptor beta3 (beta3-AR), leptin (LEP) and leptin receptor (LEPR) genes have been intensively evaluated in the search of variants that could be related to obesity and its cardiometabolic complications. The results of most of these studies have been controversial. In the present study, we investigated the relationship of the beta3-AR p.W64R, LEP c.-2548G>A and LEPR p.Q223R gene variants with body mass index (BMI), in Brazilian subjects of different genetic backgrounds and ethnic origins. Two hundred obese patients (60 males, 140 females, BMI > or = 30 kg/m2) were screened and compared to 150 lean healthy subjects (63 males, 87 females, BMI < or = 24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction. Polymerase chain reaction products were digested with specific restriction enzymes and separated by electrophoresis. There was no significant difference in the genotype frequency of the beta3-AR p.W64R and the LEP c.-2548G>A polymorphisms, between lean and obese subjects. However, the genotype and allele frequencies of the LEPR p.Q223R variant were significantly different between the normal weight and obese groups. Haplotype analysis has shown an association between the G/G allelic combination of c.-2548G>A LEP and c.668A>G LEPR, in obese subjects. Our results suggest that genetic variability in the leptin receptor is associated with body weight regulation, the LEPR p.Q223R variant being related to BMI increase. The haplotype combination of LEP c.-2548G>A and LEPR p.Q223R variants was related to a 58% increase in obesity risk.
肥胖是基因、环境、生活方式以及这些因素相互作用的综合结果。在寻找可能与肥胖及其心血管代谢并发症相关的变异体的过程中，对肾上腺素能受体β3（β3-AR）、瘦素（LEP）和瘦素受体（LEPR）基因进行了深入评估。这些研究大多结果存在争议。在本研究中，我们调查了不同遗传背景和种族起源的巴西受试者中β3-AR p.W64R、LEP c.-2548G>A和LEPR p.Q223R基因变异体与体重指数（BMI）的关系。筛选了200名肥胖患者（60名男性，140名女性，BMI≥30kg/m2），并与150名瘦的健康受试者（63名男性，87名女性，BMI≤24kg/m2）进行比较。提取基因组DNA并通过聚合酶链反应进行扩增。聚合酶链反应产物用特异性限制性酶消化并通过电泳分离。在瘦与肥胖受试者之间，β3-AR p.W64R和LEP c.-2548G>A多态性的基因型频率没有显著差异。然而，正常体重组与肥胖组之间LEPR p.Q223R变异体的基因型和等位基因频率存在显著差异。单倍型分析显示，在肥胖受试者中，c.-2548G>A LEP的G/G等位基因组合与c.668A>G LEPR之间存在关联。我们的结果表明，瘦素受体的基因变异性与体重调节相关，LEPR p.Q223R变异体与BMI增加有关。LEP c.-2548G>A和LEPR p.Q223R变异体的单倍型组合与肥胖风险增加58%有关。
