Association of GSTM1, GSTT1, and TP53 Genetic Variants with Obesity in Children

This study explores whether GSTM1, GSTT1, and TP53 rs1042522 polymorphisms, key regulators of detoxification and oxidative stress responses, influence obesity risk and related metabolic profiles in children.

Blood samples from 60 obese children and 60 healthy controls were analyzed. GSTM1 and GSTT1 deletions were assessed via polymerase chain reaction melting curve analysis, and TP53 rs1042522 was genotyped by direct DNA sequencing. Deviations from Hardy-Weinberg expectations and genotype frequencies in controls were evaluated, and the association of genetic variants with obesity, clinical complications, and metabolic parameters was examined.

In obese children, GSTM1 and GSTT1 genotype frequencies deviated from Hardy-Weinberg expectations and differed from controls, whereas TP53 rs1042522 conformed to expected distributions yet was statistically underpowered. The GSTM1 null genotype increased obesity risk 3.28-fold (95% CI: 1.36-7.93, P < .05). The GSTT1 null genotype conferred a 4.76-fold higher risk (95% CI: 2.08-10.88, P < .001). TP53 rs1042522 showed no association (OR = 1.12, 95% CI: 0.44-2.87). The GSTM1 null carriers had elevated cholesterol, low-density lipoprotein (LDL), and gamma-glutamyl transferase, while TP53 Arg/Arg and Pro/Pro carriers exhibited higher LDL and alanine aminotransferase, respectively. No significant links were observed with insulin resistance or hepatic steatosis.

The GSTM1 and GSTT1 null genotypes are significant genetic risk factors for childhood obesity, likely through reduced detoxification capacity and subsequent oxidative stress-related metabolic disruption. These findings highlight the importance of considering detoxification pathways when assessing genetic predisposition to obesity in children.