Association of Melanocortin-4 Receptor Single Nucleotide Polymorphisms rs2331841 and rs12970134 with Metabolically Unhealthy Obesity in a North Indian Cohort.

BACKGROUND

Obesity is a global epidemic with diverse metabolic outcomes, categorized as metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). Genetic variations in the MC4R gene are known to be key to energy homeostasis, making it a critical candidate for explaining this metabolic heterogeneity.

AIM: This study aimed to investigate the genetic basis of metabolically unhealthy obesity (MUHO) in a North Indian population from the Jammu region, specifically focusing on the association between polymorphisms (Single Nucleotide Polymorphisms [SNPs]) within the Melanocortin-4 Receptor (MC4R) gene and the predisposition to MUHO.

MATERIALS AND

METHODS

We analyzed a cohort of 846 adult participants from the North Indian population of the Jammu region. The participants were divided into three groups: MUHO (N = 300), MHO (N = 246), and metabolically healthy normal weight (MH-NW, N = 300). Genotyping was performed to assess the association of the two specific MC4R: rs2331841 and rs12970134.

RESULTS

Our findings revealed a statistically significant association between the "A" risk alleles of both MC4R SNPs and an increased predisposition to MUHO. The "A" allele of rs2331841 conferred a 1.75-fold increased risk for MUHO compared to MH-NW (P = 0.0008) and a 1.42-fold increased risk compared to MHO (P = 0.02). The "A" allele of rs12970134 showed a 1.60-fold increased risk for MUHO versus MH-NW (P = 0.005) and a 1.35-fold increased risk versus MHO (P = 0.057).

CONCLUSION

These results indicate that genetic variations in the MC4R gene contribute to the metabolic heterogeneity of obesity. Identifying these specific genetic markers is crucial for early risk stratification and developing personalized preventive strategies against obesity-related metabolic disorders.