Associação dos genes FTO, DRD2 e ANKK1 com risco metabólico e efeito na obesidade pediátrica: estudo tipo caso controle
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2020-07-06
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Universidade Federal de Goiás
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Background: Obesity is a complex pathology, in which behavioral, endocrinological, metabolic, genetic and epigenetic factors interact. It is known that the genetic component is responsible for up to 70% of the variation in body mass index (BMI). Genetic polymorphisms that affect dopamine availability and secretion can alter the risk of obesity.
Objectives: To determine the allele and genotype frequencies of the polymorphisms of FTO (rs9939609), DRD2 (rs6277) and ANKK1 (rs18000497) genes in children and adolescents from Goiás. To investigate the relationship between pediatric obesity, insulin sensitivity and cardiovascular risk factors (CRF) with the studied genes.
Methods: Case-Control study conducted with adolescents and children over five years. The two main groups, Obese (O) and Eutrophic (E), were subdivided according to the value of HOMA-IR into Obese with insulin resistance (ORI) or insulin sensitivity (OSI) and Eutrophic resistant (ERI) or sensitive (ESI) to insulin. According to the presence of two or more CRF, they were subdivided into metabolically unhealthy (MU) or metabolically healthy (MH) groups: OMU, OMH, EMU, EMH. Polymorphisms were determined by real-time PCR or PCR-RFLP. The SPSS program was used for statistical calculations
Results: The research assessed 124 obese and 102 eutrophic children and adolescents aged from 5 to 16 years. In the obese group, the higher the number of risk alleles of FTO and ANKK1 genes isolated and the three genes combined, the higher the mean BMI (p<0,0001). Regarding the FTO gene: the frequency of the risk allele was: 57.7%-ERI, 37.4%-ESI (p=0,048), and the homozygous wild genotype was: 29.5%-OMU, 37.5%-OMH (p=0,02). Regarding the DRD2 gene: the genotypes with the risk allele were present in 84.6%-OMU and 67.5%-OMH (p=0,031). Regarding the ANKK1 gene: the frequency of the homozygous risk genotype was current in 15.4%-ERI and 13.5%-ESI (p<0,0001) and 62.5%-EMU and 41.5%-OMH (p=0,031).
Conclusions: The risk alleles of the FTO, DRD2 and ANKK1 genes showed an additive effect on the outcome of pediatric obesity in the population of Goiás. In eutrophic individuals, the ANKK1 and FTO genes were associated with insulin resistance. The presence of risk alleles of the ANKK1 and DRD2 genes increased the risk for FRCV in eutrophic and obese individuals, respectively, while the wild allele of the FTO gene had a protective effect for FRCV in obese individuals.
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PINTO, Renata Machado. Associação dos genes FTO, DRD2 e ANKK1 com risco metabólico e efeito na obesidade pediátrica: estudo tipo caso controle. 2020. 104 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2020.