Genetic variants of leptin receptor gene (rs1137101) and obesity risk in prakriti individuals and its pathogenicity prediction using in silico approaches

Abstract Background Obesity is a major global health concern closely linked to various disorders related to metabolism. Ayurveda, a traditional Indian system of medicine, categorizes individuals into three Prakriti types, Vata, Pitta, and Kapha, based on their physiological and psychological traits. This study investigates the relationship between the rs1137101 (Q223R) polymorphism and obesity, exploring the connection through Prakriti, which integrates genomic data with traditional health concepts. Methods The study included 300 participants selected based on their responses to the questionnaire and an Ayurvedic consultation. Blood samples were collected from these individuals, and DNA was extracted and analyzed for the rs1137101 variation using the PCR–RFLP method. Principal component analysis (PCA) was used to examine clustering patterns among Prakriti, genetic variants, and body composition. Additionally, the pathogenicity of the Q223R variant was evaluated using computational tools such as PANTHER, PhD-SNP, SIFT, SNAP, META-SNP, I-Mutant 2.0, MUpro, and iStable, employing sequence- and structure-based methods. Results The prevalence of the risk allele G was 50% in the obese group, compared to 38% in the normal group. PCA indicated that Kapha Prakriti is linked to the obese group, whereas Pitta and Vata correspond to the normal group. Genotype clustering revealed that the AG genotype is associated with both Kapha and Pitta, and the AA genotype is related to all three Prakriti types. In contrast, the GG genotype lacks a distinct connection. This suggests that rs1137101 polymorphism influences metabolic profiles variably across different constitutional types. Our research identified a statistically significant association between Kapha Prakriti and obesity ( p -value < 0.01). Furthermore, in silico analyses revealed that alterations in the amino acids of the leptin receptor are pathogenic and decreased protein stability. Conclusion This study suggests that the rs1137101 polymorphism in the leptin receptor gene is a notable risk factor for obesity among individuals with Kapha Prakriti. The in silico findings indicate that the Q223R variant is pathogenic, as it destabilizes protein structures and impairs leptin receptor activity. Our study shows how Prakriti classification combines with a genetic risk assessment to demonstrate ayurgenomics’ role in personalized obesity management.