title: Association of the variations in the HSD3β gene with primary aldosteronism.
abstract: OBJECTIVE
  In mice, a lack of cryptochrome results in up-regulation of aldosterone production due to high expression of the 3β-hydroxysteroid dehydrogenases (HSD3β) gene. The HSD3β pathway might play a pivotal role in aldosterone synthesis. This study aimed to determine the association of HSD3β and HSD3β2 gene variations with primary aldosteronism in a Taiwanese population.
  
  
  METHODS
  In this case-control cohort, 688 consecutive ethnically matched unrelated individuals including 362 primary aldosteronism and 326 essential hypertension cases were recruited. Nineteen tag single-nucleotide polymorphisms (SNPs) across HSD3β1, HSD3β2, and CYP11β2 were genotyped. Expression of HSD3β mRNA and immunohistochemical stain of HSD3β in the specimens of aldosterone-producing adenoma (APA) was compared with that in nonfunctional incidentaloma.
  
  
  RESULTS
  The SNPs of rs12410453 A allele in HSD3β2 gene [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.13-3.32, P=0.018] and rs6203 C allele in the HSD3β1 gene (OR 2.21, 95% CI 1.28-3.95, P=0.006) showed significant association with primary aldosteronism, with corresponding population attributable risk of 6.7 and 30.7%, respectively. Primary aldosteronism patients of non-CC in rs6203 and non-GA in rs12401453 had lower plasma aldosterone-to-renin ratio. A haplotype in a linkage disequilibrium block containing rs6203 associated significantly with serum potassium level (OR 1.24, 95% CI 1.02-1.24, P=0.026). The expressions of HSD3β1 mRNA, HSD3β2 mRNA and HSD3β protein were increased in APA, as compared to incidentaloma.
  
  
  CONCLUSIONS
  Risk-conferring genetic variations in the HSD3β gene influenced susceptibility of primary aldosteronism. Concomitant presence of rs6203 CC and rs12410453 GA genotypes synergistically increased aldosterone-to-renin ratio.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Vin-Cent
authors.initials: VC
authors.lastname: Wu
authors.forename: Cho-Kai
authors.initials: CK
authors.lastname: Wu
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.forename: Guang-Huar
authors.initials: GH
authors.lastname: Young
authors.forename: Shann-Ching
authors.initials: SC
authors.lastname: Chen
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Wang
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Lin
authors.forename: Shuei-Liong
authors.initials: SL
authors.lastname: Lin
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Chueh
authors.forename: Kwan-Dun
authors.initials: KD
authors.lastname: Wu
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D006929:Hyperaldosteronism / Q000201:enzymology / Q000235:genetics*; D017403:In Situ Hybridization; D015810:Linkage Disequilibrium; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide
chemical_list: D017931:DNA Primers; D015096:3-Hydroxysteroid Dehydrogenases