rs12255372 variant of TCF7L2 gene is protective for obesity in Mexican children

Background and aims: Variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with type 2 diabetes in adults, but the association of TCF7L2 with weight-related traits and body fat in humans is unclear. The aim of this study was to determine the relationship between the TCF7L2 gene (rs12255372) and obese phenotype in Mexican school-age children.

Methods: The study was performed in schools in Mexico City; 186 obese and 194 control children were studied. Fasting insulin and glucose, total cholesterol, LDL-C, HDL-C and triglycerides concentration were determined. The variant rs12255372 of the TCF7L2 gene was genotyped. We used age- and sex-adjusted linear models to test for association with metabolic measurements with this variant.

Results: Genotype of the TCF7L2 rs12255372 gene was associated with lower fasting plasma glucose (p = 0.001) and lower homeostasis model assessment of insulin resistance (HOMA-R; p = 0.001) in nonobese children. Heterozygous carriers for this variant were more prevalent in lean children (32.5%) than in the obese group (23.7%), which resulted in a strong protective effect for the normal weight condition (OR = 0.56, 0.32-0.97).

Conclusions: TCF7L2 rs12255372 polymorphism protects Mexican children from obesity. Further research in other large, population-based studies is needed to replicate these findings.