Associations between VMAT1 Polymorphisms and Obesity

Obesity is a multifactorial disorder with a significant genetic component. Variants within the VMAT1 gene have been proposed to influence susceptibility to obesity. This study aimed to assess the association of two single-nucleotide polymorphisms (SNPs), rs2270637 and rs1390938, within VMAT1 with obesity risk in an Iranian population undergoing sleeve gastrectomy. A number of obese patients selected for sleeve gastrectomy were genotyped for rs2270637 and rs1390938. Genotype and allele frequencies were compared using logistic regression under different genetic models (allelic, co-dominant, and recessive). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of associations. The rs1390938 SNP showed a significant association with obesity in the allelic model, with the A allele conferring protection against obesity (OR = 0.70, 95% CI 0.55-0.88, P = 0.003). In the co-dominant model, individuals with the AA genotype had a significantly reduced risk of obesity compared to those with the GG genotype (OR = 0.20, 95% CI 0.092-0.43, P = 0.000058). Similarly, in the recessive model, the AA genotype remained protective (OR = 0.21, 95% CI 0.099-0.46, P = 0.000087). The rs2270637 SNP also showed significant associations with obesity in co-dominant and recessive models. The GG genotype was protective compared to the CC genotype (OR = 0.11, 95% CI 0.034-0.41, P = 0.001) and compared to the combined GC + CC genotypes (OR = 0.11, 95% CI 0.034-0.40, P = 0.001). Both rs1390938 and rs2270637 polymorphisms in the VMAT1 gene are significantly associated with obesity risk in the studied Iranian cohort. The findings support the role of VMAT1 as a potential genetic susceptibility locus for obesity.