Association of gene polymorphisms with body weight changes in prediabetic patients

Abstract Background: Recent research has demonstrated that Type 2 Diabetes (T2D) risk is influenced by a number of common polymorphisms, including rs17782313 MC4R, rs1801282 PPARG, and rs7903146 TCF7L2. Knowledge of the association between these SNPs (single nucleotide polymorphism) and body weight changes in different forms of prediabetes treatment is still limited. The aim of this study was to investigate the association of polymorphisms within the MC4R, PPARG, TCF7L2 genes on the risk of carbohydrate metabolism disorders and body composition changes in overweight or obese patients with early carbohydrate metabolism disorders. Methods and Results: From 327 patients, a subgroup of 81 prediabetic female patients (48.7±14.8 years) of Eastern European descent participated in a 3-month study comprised of diet therapy or diet therapy accompanied with metformin treatment. Bioelectrical impedance analysis and genotyping of rs17782313 MC4R, rs7903146 TCF7L2, rs1801282 PPARG were performed. The MC4R CC and TCF7L2 TT genotypes were associated with increased risk of T2D (OR=1.46, p=0.05 and OR=2.47, p=0.006, respectively). PPARG СС homozygotes experienced increased weight loss; however, no additional improvements were experienced with the addition of metformin. MC4R ТТ homozygotes who took metformin alongside dietary intervention experienced increased weight loss and reductions in fat mass (p<0.05).Conclusions: We confirmed the previous association of the MC4R C and TCF7L2 T alleles with T2D risk. The obesity-protective alleles (MC4R T and PPARG C) were positively associated with weight loss efficiency.