title: Interactions between the FTO and GNB3 genes contribute to varied clinical phenotypes in hypertension.
abstract: BACKGROUND
  The genes FTO and GNB3 are implicated in essential hypertension but their interaction remains to be explored. This study investigates the role of interaction between the two genes in the pathophysiology of essential hypertension.
  
  
  RESULTS
  In a case-control study comprising 750 controls and 550 patients, interaction between the polymorphisms of FTO and GNB3 was examined using multifactor dimensionality reduction (MDR). The influence of interaction on clinical phenotypes like systolic and diastolic blood pressure, mean arterial pressure and body mass index was also investigated. The 3-locus MDR model comprising FTO rs8050136C/A and GNB3 rs1129649T/C and rs5443C/T emerged as the best disease conferring model. Moreover, the interacted-genotypes having either 1, 2, 3, 4 or 5 risk alleles correlated with linearly increasing odds ratios of 1.91 (P = 0.027); 3.93 (P = 2.08E-06); 4.51 (P = 7.63E-07); 7.44 (P = 3.66E-08) and 11.57 (P = 1.18E-05), respectively, when compared with interacted-genotypes devoid of risk alleles. Furthermore, interactions among haplotypes of FTO (H1-9) and GNB3 (Ha-d) differed by >1.5-fold for protective-haplotypes, CTGGC+TC [H2+Ha] and CTGAC+TC [H4+Ha] (OR = 0.39, P = 0.003; OR = 0.22, P = 6.86E-05, respectively) and risk-haplotypes, AAAGC+CT [H3+Hc] and AAAGC+TT [H3+Hd] (OR = 2.91, P = 9.98E-06; OR = 2.50, P = 0.004, respectively) compared to individual haplotypes. Moreover, the effectiveness of gene-gene interaction was further corroborated with a 1.29-, 1.25- and 1.38-fold higher SBP, MAP and BMI, respectively, in patients having risk interacted-haplotype H3+Hc and 2.48-fold higher SBP having risk interacted-haplotype H3+Hd compared to individual haplotypes.
  
  
  CONCLUSIONS
  Interactions between genetic variants of FTO and GNB3 influence clinical parameters to augment hypertension.
authors.affiliation: Functional Genomics Unit, Council of Scientific and Industrial Research -Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.forename: Samantha
authors.initials: S
authors.lastname: Kohli
authors.forename: Perwez
authors.initials: P
authors.lastname: Alam
authors.forename: Ritankur
authors.initials: R
authors.lastname: Barkotoky
authors.forename: Mohit
authors.initials: M
authors.lastname: Gupta
authors.forename: Sanjay
authors.initials: S
authors.lastname: Tyagi
authors.forename: S K
authors.initials: SK
authors.lastname: Jain
authors.forename: M A Qadar
authors.initials: MA
authors.lastname: Pasha
mesh_terms: D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C454420:G-protein beta3 subunit; D011506:Proteins; D014157:Transcription Factors; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D020962:Heterotrimeric GTP-Binding Proteins