title: Contrasting associations between aldosterone synthase gene polymorphisms and essential hypertension in blacks and in whites.
abstract: BACKGROUND
  Genetic variability in the gene for aldosterone synthase--a key enzyme in the production of aldosterone--can affect sodium homeostasis and thereby blood pressure. The possibility of impaired aldosterone production for the development of hypertension is of particular relevance in black Afro-Caribbeans exposed to a high dietary sodium intake.
  
  
  OBJECTIVE
  To compare the frequency of three variants (-344C/T, intron 2 conversion, and the K173R polymorphism) of the aldosterone synthase gene in blacks and whites, and to determine any association of the variants with hypertension.
  
  
  METHODS
  We made case-control comparisons of the three gene variants in relation to ethnic background and to essential hypertension in 193 white (51% hypertensive) and 245 black individuals (59% hypertensive) living in south London.
  
  
  RESULTS
  The frequency of each of the variants was significantly different between the two ethnic groups. The T and the K alleles were more frequent in the black participants (79 compared with 50% for the -344T allele and 81 compared with 50% for K173 allele), whereas the frequency of the intron 2 conversion allele was much lower in that group (8 compared with 38%). None of these variants was associated with essential hypertension in the black participants. In contrast, in the white participants there was a significant and graded association between the intron 2 conversion allele and essential hypertension (odds ratio 1.86, 95% confidence interval 1.16 to 2.98; = 0.01). Moreover, among the white population, the presence of homozygosity both of the T allele and of the intron 2 conversion alleles was associated with a much greater frequency of hypertension (71 compared with 43%; chi(2) = 0.03).
  
  
  CONCLUSIONS
  The contrasting associations between these variants and essential hypertension do not necessarily exclude the possibility that other, as yet undefined, variants of the aldosterone synthase gene could be linked with hypertension in black people. Nonetheless, the strong association between the intron 2 conversion allele and essential hypertension in the white population reinforces the view that the increased blood pressure may be due, at least in part, to abnormal expression of enzymes involved in the metabolism of adrenal mineralocorticoids.
authors.affiliation: Blood Pressure Unit, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Haidong
authors.initials: H
authors.lastname: Zhu
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Sagnella
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Dong
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Miller
authors.forename: Abiodun
authors.initials: A
authors.lastname: Onipinla
authors.forename: Nirmala D
authors.initials: ND
authors.lastname: Markandu
authors.forename: Graham A
authors.initials: GA
authors.lastname: MacGregor
mesh_terms: D000225:Adenine; D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000208:ethnology* / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D013941:Thymine; D044465:White People / Q000235:genetics*
chemical_list: D019405:Cytochrome P-450 CYP11B2; D000225:Adenine; D013941:Thymine