title: Multi-locus interactions of vascular homeostasis genes in essential hypertension: a gender-based study.
abstract: BACKGROUND
  Studies on genes of endothelial and vascular homeostasis are inadequate in females.
  
  
  METHODS
  We investigated the role of 7 variants of ACE, AGT and NOS3 and their correlation with NO(x) levels and ACE activity in hypertension susceptibility in 910 case-controls of both genders.
  
  
  RESULTS
  Prevalence of alleles D of ACE I/D; -6A of AGT -6G/A; -786C, 894T and 4a of NOS3 -786T/C, 894G/T and 4b/4a polymorphisms was observed in patients (P< or =0.05). The 3 genotypes-combinations containing 6+5 wild-type alleles of AGT and NOS3 were significantly less prevalent in patients (P< or =0.0003). The haplotypes 235T/174T/-6A of AGT (P=4E-3) and -786T/894G/4a and -786C/894G/4a of NOS3 (P=2E-3, P=0.011, respectively) were significantly more prevalent in patients. The AGT and NOS3 findings were similar in males. Genotypes-combinations with 6+5 wild-type alleles of AGT correlated with higher NO(x) levels (P=0.03). The NOS3 genotypes-combinations having 6 and 6+5 wild-type alleles correlated with decreased ACE activity (P=0.025, P=0.0015, respectively) and increased NO(x) levels (P=0.001, P=0.0001, respectively) in patients. In gene-gene interactions, ACE D allele associated with < or =4 wild-type alleles containing genotypes-combinations of AGT and NOS3 in patients (P< or =0.04).
  
  
  CONCLUSIONS
  Within gene and between genes interactions of variants influence ACE activity and NO(x) levels and associate with EH.
authors.affiliation: Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.forename: Azim
authors.initials: A
authors.lastname: Nejatizadeh
authors.forename: Ehtesham
authors.initials: E
authors.lastname: Arif
authors.forename: Salman
authors.initials: S
authors.lastname: Akhtar
authors.forename: Mohit
authors.initials: M
authors.lastname: Gupta
authors.forename: Sanjay
authors.initials: S
authors.lastname: Tyagi
authors.forename: A K
authors.initials: AK
authors.lastname: Goyal
authors.forename: S K
authors.initials: SK
authors.lastname: Jain
authors.forename: M A
authors.initials: MA
authors.lastname: Qadar Pasha
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D012727:Sex Characteristics