title: Polymorphisms of the insertion / deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data.
abstract: BACKGROUND
  Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects. The present study examines how polymorphisms of the insertion/deletion (I/D) ACE and M235T AGT genes account for presence and severity of hypertension, and embeds the data in a meta-analysis of relevant studies.
  
  
  METHODS
  The I/D polymorphisms of the ACE and M235T polymorphisms of the AGT genes were determined by RFLP (restriction fragment length polymorphism) and restriction analysis in 638 hypertensive patients and 720 normotensive local blood donors in Weisswasser, Germany. Severity of hypertension was estimated by the number of antihypertensive drugs used.
  
  
  RESULTS
  No difference was observed in the allele frequencies and genotype distributions of ACE gene polymorphisms between the two groups, whereas AGT TT homozygotes were more frequent in controls (4.6% vs. 2.7%, P = .08). This became significant (p = 0.035) in women only. AGT TT genotype was associated with a 48% decrease in the risk of having hypertension (odds ratio: 0.52; 95% CI, 0.28 to 0.96), and this risk decreased more significantly in women (odds ratio: 0.28; 95% CI, 0.1 to 0.78). The meta-analysis showed a pooled odds ratio for hypertension of 1.21 (TT vs. MM, 95% CI: 1.11 to 1.32) in Caucasians. No correlation was found between severity of hypertension and a specific genotype.
  
  
  CONCLUSIONS
  The ACE I/D polymorphism does not contribute to the presence and severity of essential hypertension, while the AGT M235T TT genotype confers a significantly decreased risk for the development of hypertension in the population studied here. This contrasts to the findings of meta-analyses, whereby the T allele is associated with increased risk for hypertension.
authors.affiliation: Bioinformatics Institute, Singapore. mondry@hotmail.com
authors.forename: Adrian
authors.initials: A
authors.lastname: Mondry
authors.forename: Marie
authors.initials: M
authors.lastname: Loh
authors.forename: Pengbo
authors.initials: P
authors.lastname: Liu
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Zhu
authors.forename: Mato
authors.initials: M
authors.lastname: Nagel
mesh_terms: D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D003430:Cross-Sectional Studies; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008715:Methionine; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D013912:Threonine
chemical_list: D004251:DNA Transposable Elements; D000808:Angiotensinogen; D013912:Threonine; D008715:Methionine; D007703:Peptidyl-Dipeptidase A