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Introduction Peroxisome proliferator-activated receptor gamma (PPARG) gene polymorphisms, particularly rs1801282 (Pro12Ala) and rs3856806 (C161T), have been implicated in obesity, but findings remain inconsistent across populations. This study investigated their association with obesity and haplotype structures among South Indian young adults.Methods A cross-sectional genetic association study was conducted in 372 healthy young adults (186 with obesity, 186 without), aged 18–25 years. Anthropometric parameters were recorded, and genotyping for rs1801282 and rs3856806 was performed using Tetra-Primer ARMS-PCR. Statistical analyses included allele and genotype frequency comparison, Fisher’s exact test, haplotype analysis, receiver operating characteristic curves and scatter plot analysis. The number needed to genotype (NNG) was estimated for rs1801282.Results The rs1801282 G allele showed a significant association with obesity (p<0.0001), with GG genotype carriers having higher odds (OR=2.82; 95% CI 1.7 to 4.6). Individuals with the G allele had higher body mass index and central adiposity. The rs3856806 variant was not associated with obesity but showed a nominal effect on waist–hip ratio. Haplotype analysis revealed Haplo-3 (G–C) as exclusive to obese individuals and Haplo-2 (C–T) as exclusive to non-obese participants, indicating potential risk and protective roles, respectively. Obese individuals exhibited numerically greater haplotype diversity (Hₑ = 0.509 vs 0.396) and a higher number of private haplotypes. However, this difference was not statistically significant (p=0.14), as determined by a permutation test. The estimated NNG was 4, suggesting that screening four individuals for the G allele may identify one at elevated genetic risk.Conclusion The PPARG rs1801282 polymorphism and specific haplotypes are associated with obesity in South Indian young adults. These findings should be interpreted with caution and may guide future genetic epidemiology studies rather than immediate clinical applications.