title: The epistasis between vascular homeostasis genes is apparent in essential hypertension.
abstract: OBJECTIVE
  The epistasis influence of vascular homeostasis genes is vital to multigenetic diseases. This study was designed to perceive the possible role of epistasis in the etiology of essential hypertension.
  
  
  METHODS
  We investigated seven polymorphisms of ACE, CYP11B2 and NOS3 epistatically, and SBP, DBP, MAP, ACE activity, plasma aldosterone concentration (PAC) and NOx level in 860 age- and ethnicity-matched unrelated north-Indian subjects.
  
  
  RESULTS
  The hypertension risk in individuals with interacted-genotypes (IwIw+IwIc)+(4aa), (IcIc)+(4bb+4ba) and IcIc+4aa of the CYP11B2 and NOS3 was significantly higher with odds ratio 5.5 (95% CI=2.9-10.6, P<0.0001), 2.4 (95% CI=1.4-4.1, P<0.0008) and 7.5 (95% CI=1.6-34.8, P=0.010), respectively. The odds ratio for hypertension with interacted-haplotypes (-344T/Ic)+(-922A/-786T/4a/894G) and (-344T/Ic)+(-922G/-786C/4a/894G) of CYP11B2 and NOS3 was 5.3 (95% CI=2.0-14.2, P=0.005) and 3.9 (95% CI=1.4-10.4, P=0.04), respectively; whereas for the protective interacted-haplotypes (-344T/Iw)+(-922A/-786T/4b/894G), the odds ratio was 0.7 (95% CI=0.5-0.9, P=0.03). While the interacted-genotypes, IcIc+4aa correlated with higher SBP and MAP (P=0.006; P=0.04), the interacted-haplotypes, (-344T/Ic)+(-922A/-786T/4a/894G) and (-344T/Ic)+(-922G/-786C/4a/894G) correlated with higher MAP and lower NOx level (P=0.02 and P=0.03, respectively), and the protective interacted-haplotypes (-344T/Iw)+(-922A/-786T/4b/894G) correlated with lower PAC and MAP (P=0.024 and P=0.018, respectively).
  
  
  CONCLUSIONS
  The epistasis between CYP11B2 and NOS3 and its correlation with varied clinical and biochemical parameters signify its possible contribution in the complex etiology of hypertension.
authors: Functional Genomics Unit, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India.
authors: Rahul
authors: R
authors: Kumar
authors: Azim
authors: A
authors: Nejatizadeh
authors: Mohit
authors: M
authors: Gupta
authors: Amandeep
authors: A
authors: Markan
authors: Sanjay
authors: S
authors: Tyagi
authors: S K
authors: SK
authors: Jain
authors: M A Qadar
authors: MA
authors: Pasha
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D000450:Aldosterone; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A