IGF2, LEPR, POMC, PPARG, and PPARGC1 gene variants are associated with obesity-related risk phenotypes in Brazilian children and adolescents.
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.
Departamento de Nutrição Clínica e Social, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil.
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EM
Queiroz
Departamento de Nutrição, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brasil.
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AP
Cândido
Departamento de Farmácia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil.
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IM
Castro
Departamento de Nutrição Clínica e Social, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil.
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AQ
Bastos
Escola de Medicina, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil.
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GL
Machado-Coelho
Departamento de Nutrição Clínica e Social, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil.
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RN
Freitas
D000293:Adolescent; D000704:Analysis of Variance; D000886:Anthropometry; D001938:Brazil; D002318:Cardiovascular Diseases / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D009765:Obesity / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D050177:Overweight / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics
C035170:IGF2 protein, human; D047495:PPAR gamma; D054411:Receptors, Leptin; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D011333:Pro-Opiomelanocortin; D007335:Insulin-Like Growth Factor II; D002784:Cholesterol