title: Association of FTO and IRX3 genetic variants to obesity risk in north India.
abstract: BACKGROUND
  Obesity is an increasingly important health problem worldwide as well as in developing countries like India. Recent genetic studies suggest that obesity associated FTO and IRX3 are functionally linked and many effects due to genetic variants in FTO gene act through IRX3.
  
  
  OBJECTIVE
  To evaluate the association of FTO and IRX3 genetic variants towards obesity risk.
  
  
  METHODS
  North Indian individuals categorised as non-obese (BMI < 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)) were selected. FTO rs8050136, rs1421085, rs9939609, rs17817449 and IRX3 rs3751723 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, FTO rs8050136 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); FTO rs1421085 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); FTO rs9939609 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 of FTO rs17817449 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 of IRX3 rs3751723 were significantly associated with obesity. In multi-locus analysis, SNPs of FTO and IRX3 were in strong linkage disequilibrium and in haplotype and GMDR analysis the SNPs were significantly associated with obesity risk (p < 0.05).
  
  
  CONCLUSIONS
  This is the first study to reveal that genetic variants of both FTO and IRX3 genes are in high linkage disequilibrium (LD) and are associated with obesity risk in North Indians.
authors.affiliation: a Department of Physiology , King George's Medical University , Chowk, Lucknow, Uttar Pradesh , India .|b Department of Medical Genetics , Sanjay Gandhi Post Graduate Institute of Medical Sciences , Lucknow, Uttar Pradesh , India .
authors.forename: Apurva
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: b Department of Medical Genetics , Sanjay Gandhi Post Graduate Institute of Medical Sciences , Lucknow, Uttar Pradesh , India .
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
authors.affiliation: a Department of Physiology , King George's Medical University , Chowk, Lucknow, Uttar Pradesh , India .
authors.forename: Jai
authors.initials: J
authors.lastname: Prakash
authors.affiliation: c Darbhanga Medical College and Hospital, Karpuri Chowk, Benta Laheriasarai, Darbhanga, Bihar , India , and.
authors.forename: Pranjal
authors.initials: P
authors.lastname: Srivastava
authors.affiliation: d Sikkim Manipal Institute of Medical Sciences (SMIMS) , Upper Tadong, Tadong, Gangtok, Sikkim , India.
authors.forename: Nimisha
authors.initials: N
authors.lastname: Srivastava
authors.affiliation: a Department of Physiology , King George's Medical University , Chowk, Lucknow, Uttar Pradesh , India .
authors.forename: Neena
authors.initials: N
authors.lastname: Srivastava
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008297:Male; D058011:Multifactor Dimensionality Reduction; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C501598:IRX3 protein, human; D014157:Transcription Factors; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
keywords: Linkage disequilibrium; generalised multifactor dimensionality reduction; haplotypes