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.

METHOD:

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.

CONCLUSION:

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: Vin-Cent Wu, Cho-Kai Wu, Yi-Cheng Chang, Guang-Huar Young, Shann-Ching Chen, Wei-Shiung Yang, Chien-Yuan Chen, Wei-Jie Wang, Chien-Yu Lin, Yen-Hung Lin, Shuei-Liong Lin, Shih-Chieh Chueh, Kwan-Dun Wu, TAIPAI study group
• Journal: Journal of hypertension (J Hypertens) Vol. 31 Issue 7 Pg. 1396-405; discussion 1405 (Jul 2013) ISSN: 1473-5598 [Electronic] Netherlands
• PMID: 24006038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• 3-Hydroxysteroid Dehydrogenases

Topics

• 3-Hydroxysteroid Dehydrogenases (genetics)
• Base Sequence
• DNA Primers
• Genotype
• Humans
• Hyperaldosteronism (enzymology, genetics)
• In Situ Hybridization
• Linkage Disequilibrium
• Multigene Family
• Polymorphism, Single Nucleotide