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Background: Obesity is an increasingly important health problem worldwide as well as in developing countries like India. Recent genetic studies suggest that obesity associatedFTOandIRX3are functionally linked and many effects due to genetic variants inFTOgene act throughIRX3. Aim: To evaluate the association ofFTOandIRX3genetic variants towards obesity risk. Subjects and methods: North Indian individuals categorised as non-obese (BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2) were selected.FTOrs8050136, rs1421085, rs9939609, rs17817449 andIRX3rs3751723 were genotyped by means of validated Taqman® allelic discrimination to evaluate their association with obesity by means of single locus logistic regression by SPSS ver. 19 and multi-locus linkage and haplotype analysis by SNPStats and gene–gene interaction with Generalised Multifactor Dimensionality Reduction (GMDR) ver.6. Results: In single locus analysis,FTOrs8050136 CA (p = 0.0001; OR (95% CI) = 2.4 (1.7–3.4) and AA (p = 0.0001; OR (95% CI) = 3.1 (1.9–5.2);FTOrs1421085 TA (p = 0.0001; OR (95% CI) = 2.1 (1.4–3.0) and AA (p = 0.0001; OR (95% CI) = 3.0 (1.8–5.0);FTOrs9939609 TC (p = 0.0001; OR (95% CI) = 2.1 (1.5–3.1) and CC (p = 0.0001; OR (95% CI) = 4.2 (2.5–7.3) along with TG (p = 0.001; OR (95% CI) = 2.1 (1.3–3.2) and GG (p = 0.021; OR (95% CI) = 3.8 (1.2–11.8) genotypes ofFTOrs17817449 with GT (p = 0.0001; OR (95% CI) = 2.1 (1.5–3.1) and TT (p = 0.012; OR (95% CI) = 3.3 (1.8–3.6) genotypes ofIRX3rs3751723 were significantly associated with obesity. In multi-locus analysis, SNPs ofFTOandIRX3were in strong linkage disequilibrium and in haplotype and GMDR analysis the SNPs were significantly associated with obesity risk (p < 0.05). Conclusion: This is the first study to reveal that genetic variants of bothFTOandIRX3genes are in high linkage disequilibrium (LD) and are associated with obesity risk in North Indians. [ABSTRACT FROM AUTHOR]

Background: Obesity is a multi-factorial disorder influenced by genetic and environmental factors. The physiological pathways associated with obesity are complex and involve several genes. Aim: The aim of this survey is to evaluate the association of genetic variants of melanocortin-4-receptor (MC4R), pro-opiomelanocortin (POMC), apolipoprotein E (APOE) and agouti-related protein (AGRP) with obesity in the North Indian population. Methods: MC4R rs17782313, POMC rs1042571, APOE-Hha1and AGRP rs3412352 polymorphisms were investigated for their association in 396 obese individuals with BMI ≥ 30 kg/m2and 300 healthy non-obese individuals with BMI < 30 kg/m2. Genotyping was performed using Taqman probes and PCR-RFLP methods. Single locus logistic regression analysis was conducted using (SPSS), ver.19 and PLINK software Version 1.01 and high order genetic interactions associated with obesity risk were analysed using MDR software (version 2.3.0.2). Results: The genotypes of MC4R rs17782313, POMC rs1042571 and APOE-Hha1were significantly associated with obese individuals (BMI ≥ 30 kg/m2) when compared with non-obese individuals (BMI < 30 kg/m2). No association of AGRP rs34123523 was seen with obesity. Conclusions: The best interaction model for predicting obesity risk by MDR analysis was the three factor model including POMC (C > T), MC4R (T > C) and APOE (Hha1) polymorphisms. Genetic variants in MC4R, POMC and APOE genes might play significant roles in predisposing obesity (BMI ≥ 30 kg/m2) in the North Indian population. [ABSTRACT FROM PUBLISHER]