Association of Fat Mass and Obesity Associated, Dopamine Receptor Type 2 and Ankyrin Repeat and Kinase Domain Containing 1 Genes with Pediatric Obesity and Metabolic Risk: A Case-Control Study

Abstract

Background Genetic polymorphisms that affect the availability and secretion of dopamine can affect the risk of obesity. Objectives To investigate the relationship between pediatric obesity and cardiovascular risk factors (CRF) with the polymorphisms of “Fat Mass and Obesity Associated” (FTO) rs9939609, “Dopamine Receptor type 2” (DRD2) rs6277 and “Ankyrin Repeat and Kinase Domain Containing 1” (ANKK1) rs18000497 genes. Methods Case-Control study conducted with 226 pediatric patients from 5 to 16-years of age. 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 or metabolically healthy groups: Obese Metabolically Unhealthy (OMU), Obese Metabolically Healthy (OMH), Eutrophic Metabolically Unhealthy (EMU) and Eutrophic Metabolically Healthy (EMH). Polymorphisms were determined by real-time Polymerase Chain Reaction (PCR) or Restriction Fragment Length Polymorphisms (PCR-RFLP). Results 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). Conclusion Risk alleles of FTO, DRD2 and ANKK1 genes had an additive effect on the outcome of pediatric obesity in Brazilian children and conferred a higher risk of insulin resistance (FTO and ANKK1) and CRF.