Queiroz E M, Cândido A P C, Castro I M, Bastos A Q A, Machado-Coelho G L L, Freitas R N
Departamento de Nutrição Clínica e Social, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil.
Departamento de Nutrição, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brasil.
Braz J Med Biol Res. 2015 Jul;48(7):595-602. doi: 10.1590/1414-431X20154155. Epub 2015 Apr 28.
Association studies of genetic variants and obesity and/or obesity-related risk factors have yielded contradictory results. The aim of the present study was to determine the possible association of five single-nucleotide polymorphisms (SNPs) located in the IGF2, LEPR, POMC, PPARG, and PPARGC1 genes with obesity or obesity-related risk phenotypes. This case-control study assessed overweight (n=192) and normal-weight (n=211) children and adolescents. The SNPs were analyzed using minisequencing assays, and variables and genotype distributions between the groups were compared using one-way analysis of variance and Pearson's chi-square or Fisher's exact tests. Logistic regression analysis adjusted for age and gender was used to calculate the odds ratios (ORs) for selected phenotype risks in each group. No difference in SNP distribution was observed between groups. In children, POMC rs28932472(C) was associated with lower diastolic blood pressure (P=0.001), higher low-density lipoprotein (LDL) cholesterol (P=0.014), and higher risk in overweight children of altered total cholesterol (OR=7.35, P=0.006). In adolescents, IGF2 rs680(A) was associated with higher glucose (P=0.012) and higher risk in overweight adolescents for altered insulin (OR=10.08, P=0.005) and homeostasis model of insulin resistance (HOMA-IR) (OR=6.34, P=0.010). PPARG rs1801282(G) conferred a higher risk of altered insulin (OR=12.31, P=0.003), and HOMA-IR (OR=7.47, P=0.005) in overweight adolescents. PARGC1 rs8192678(A) was associated with higher triacylglycerols (P=0.005), and LEPR rs1137101(A) was marginally associated with higher LDL cholesterol (P=0.017). LEPR rs1137101(A) conferred higher risk for altered insulin, and HOMA-IR in overweight adolescents. The associations observed in this population suggested increased risk for cardiovascular diseases and/or type 2 diabetes later in life for individuals carrying these alleles.
基因变异与肥胖及/或肥胖相关风险因素的关联研究得出了相互矛盾的结果。本研究的目的是确定位于IGF2、LEPR、POMC、PPARG和PPARGC1基因中的五个单核苷酸多态性（SNP）与肥胖或肥胖相关风险表型之间的可能关联。这项病例对照研究评估了超重（n = 192）和体重正常（n = 211）的儿童和青少年。使用微测序分析法对SNP进行分析，并使用单因素方差分析以及Pearson卡方检验或Fisher精确检验比较两组之间的变量和基因型分布。采用针对年龄和性别的逻辑回归分析来计算每组选定表型风险的比值比（OR）。两组之间未观察到SNP分布存在差异。在儿童中，POMC rs28932472（C）与较低的舒张压（P = 0.001）、较高的低密度脂蛋白（LDL）胆固醇（P = 0.014）以及超重儿童总胆固醇改变的较高风险相关（OR = 7.35，P = 0.006）。在青少年中，IGF2 rs680（A）与较高的血糖（P = 0.012）以及超重青少年胰岛素改变（OR = 10.08，P = 0.005）和胰岛素抵抗稳态模型（HOMA - IR）（OR = 6.34，P = 0.010）的较高风险相关。PPARG rs1801282（G）使超重青少年胰岛素改变（OR = 12.31，P = 0.003）和HOMA - IR（OR = 7.47，P = 0.005）的风险更高。PARGC1 rs8192678（A）与较高的甘油三酯相关（P = 0.005），而LEPR rs1137101（A）与较高的LDL胆固醇存在边缘关联（P = 0.017）。LEPR rs1137101（A）使超重青少年胰岛素改变和HOMA - IR的风险更高。在这一人群中观察到的关联表明，携带这些等位基因的个体在晚年患心血管疾病和/或2型糖尿病的风险增加。
