Objective: We studied multi-loci variants to identify the contribution of six candidate genes (ADIPOQ, CDH13, LYPLAL1, MC4R, PPARG and PGC1A) in the development of obesity and overweight.
Design: We genotyped 404 chromosomes with eleven SNPs in Mexican female adolescents, who were subdivided into two groups (obesity-overweight and normal-weight) using the World Health Organization parameters. Genomic (800 chromosomes) and ancestral (208 chromosomes) controls were included to reduce the population bias. Anthropometric measurements, biochemical parameters, and caloric intake were obtained only in the groups of Mexican female adolescents.
Results: A positive genotype-phenotype association was found that involves the multi-allelic combination of three risk alleles (one in PPARG and two in LYPLAL1) with obesity and overweight (OR=3.1, P=.010). This combination also exhibited a significant association with waist circumference (P=.030) and triglycerides levels (P=.030). These associations were supported by a logistic regression analysis adjusted for several confounding variables.
Conclusions: Our data suggest the joint participation of PPARG-LYPLAL1 genes in metabolic disorders development. Hence, these genes could act as potential biomarkers in obesity and overweight. Our findings underscore the complexity of metabolic disorders and provide evidence about the importance of multi-loci analysis to study complex diseases.
Keywords: LYPLAL1; PPARG; ADIPOQ; MC4R; CDH13;; Mexico; Multi-allelic Combination; Obesity.