FTO 和 UCP-1 SNPs 对巴西个体中极度肥胖、糖尿病和心血管风险的贡献。
The contribution of FTO and UCP-1 SNPs to extreme obesity, diabetes and cardiovascular risk in Brazilian individuals.
机构信息
Department of Surgery, School of Medicine, Universidade Federal de Minas Gerais, Av, Alfredo Balena 190, Belo Horizonte, 30130-100, Brazil.
出版信息
BMC Med Genet. 2012 Nov 7;13:101. doi: 10.1186/1471-2350-13-101.
BACKGROUND
Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported.
METHODS
To assess the putative contribution of both FTO and UCP-1 to body mass index (BMI) and cardiovascular risk we genotyped SNPs rs9939609 (FTO) and rs6536991, rs22705565 and rs12502572 (UCP-1) from 126 morbidly obese subjects (BMI 42.9 ± 5.6 kg/m2, mean ± SE) and 113 normal-weight ethnically matched controls (BMI 22.6 ± 3.5 kg/m2, mean ± SE). Waist circumference, blood pressure, glucose and serum lipids were also measured. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels) for ethnic assignment and to estimate the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population.
RESULTS
Cases did not differ from controls in the proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991 were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An allele dose dependent tendency was observed for BMI for rs6536991 sample of controls. No other significant associations between any SNP and hypertension, hyperlipidemia and diabetes were noted after correction for BMI and no significant synergistic effect between FTO and UCP-1 SNPs with obesity were noted. There was not an association between rs9939609 (FTO) and rs6536991 (UCP-1) in with maximum weight loss after 1 year in 94 obese patients who underwent bariatric surgery.
CONCLUSION
Our data are consistent with FTO rs9939609 and UCP-1 rs6536991 common variants as contributors to obesity in the Brazilian population.
背景
肥胖已成为一种常见的人类疾病，与显著的发病率和死亡率以及生活质量下降有关。在肥胖的白种人群体中，两个候选基因 FTO 和 UCP-1 的序列变异已被报道存在过度表达。然而，这些基因多态性与巴西这样的多民族群体中肥胖表型的关联尚未被报道。
方法
为了评估 FTO 和 UCP-1 基因对体重指数（BMI）和心血管风险的潜在贡献，我们对 126 名病态肥胖患者（BMI 42.9±5.6kg/m2，平均值±SE）和 113 名体重正常的、种族匹配的对照组（BMI 22.6±3.5kg/m2，平均值±SE）进行了 FTO 基因 rs9939609 和 UCP-1 基因 rs6536991、rs22705565 和 rs12502572 的单核苷酸多态性（SNP）基因分型。还测量了腰围、血压、血糖和血清脂质。每个样本还进行了 40 个双等位基因短插入/缺失多态性（indels）的基因分型，以进行种族归属，并估计巴西人群中欧洲、非洲和美洲原住民的生物地理祖先比例。
结果
病例组和对照组的基因组祖先比例没有差异。FTO 基因 SNP rs9939609 和 UCP-1 基因 SNP rs6536991 与 BMI 显著相关（p=0.04 和 p<0.0001）。对照组 rs6536991 样本中观察到等位基因剂量依赖性趋势。在对 BMI 进行校正后，没有发现任何其他 SNP 与高血压、高血脂和糖尿病之间存在显著关联，也没有发现 FTO 和 UCP-1 SNP 之间存在显著的协同作用与肥胖有关。在 94 名接受减重手术的肥胖患者中，我们没有发现 rs9939609（FTO）与 rs6536991（UCP-1）与 1 年后最大体重减轻之间存在关联。
结论
我们的数据表明，FTO 基因 rs9939609 和 UCP-1 基因 rs6536991 常见变异是巴西人群肥胖的原因之一。
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