Interaction of GCKR, MLXIPL and FADS genes polymorphisms with obesity in the occurrence of childhood metabolic syndrome

Abstract

Objective: Considering the implication of better understanding of metabolic syndrome (MetS) pathophysiology in designing proper preventative and management strategies and the fact that dyslipidemia is one of the early and common features of MetS, the aim of this study was to investigate the interaction of some lipid regulatory genes polymorphisms with obesity in the occurrence of MetS in children. Methods: In this nested case-control study, 300 frozen samples of normal weight and 300 samples of overweight/obese children aged 10-18 years old from the CASPIAN III study samples were selected randomly. The studied population was classified into four groups as follows: Normal weight participants with and without MetS and overweight/obese participants with and without MetS. Allelic and genotypic frequencies of GCKR (rs780094), GCKR(rs1260333), MLXIPL(rs3812316) and FADS(rs174547) polymorphisms were determined and compared in the four studied groups. Interaction of each studied Single Nucleotide Polymorphisms (SNPs) with obesity in the occurrence of MetS was evaluated also. Results: In this study, 276 normal weight and 252 overweight/obese children were evaluated. Frequency of minor alleles of GCKR (rs780094) polymorphism in normal weight students with MetS was significantly higher than normal weight students without MetS (P=0.04), obese students without MetS (P=0.04) and obese students with MetS(P=0.03). Frequency of cc allele of MLXIPL (rs3812316) polymorphism in normal weight students with MetS was significantly higher than obese children with MetS (P=0.04). The interaction of each studied SNPs with obesity had significant effect in the occurrence of MetS (P<0.001). Conclusion: In this study, we identified two SNPs which possibly are in association with metabolically unhealthy normal weight phenotype. The interaction of lipid regulatory gene polymorphisms with obesity result in the occurrence of MetS, whereas in each of the studies SNPs were not associated with MetS. Identification of such interactions between modifiers like obesity with genetic variants could be helpful in development of preventative strategies for reducing the increasing trend of MetS in children.