Association of FTO and IRX3 genetic variants to obesity risk in north India.

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]