Multi-locus interactions of vascular homeostasis genes in essential hypertension: a gender-based study

Clin Chim Acta. 2009 Jul;405(1-2):87-93. doi: 10.1016/j.cca.2009.04.010. Epub 2009 Apr 18.


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).

Conclusion: Within gene and between genes interactions of variants influence ACE activity and NO(x) levels and associate with EH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Genotype
  • Homeostasis*
  • Humans
  • Hypertension / epidemiology*
  • Hypertension / genetics*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics
  • Risk Factors
  • Sex Characteristics*