Journal of Hypertension

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Journal of Hypertension:
doi: 10.1097/HJH.0b013e328360ef3c
ORIGINAL PAPERS: Genetic aspects

Association of the variations in the HSD3β gene with primary aldosteronism

Wu, Vin-Centa,*; Wu, Cho-Kaia; Chang, Yi-Chengc; Young, Guang-Huarb; Chen, Shann-Chingd; Yang, Wei-Shiunga; Chen, Chien-Yuana; Wang, Wei-Jiee; Lin, Chien-Yuf; Lin, Yen-Hunga,*; Lin, Shuei-Lionga; Chueh, Shih-Chiehg; Wu, Kwan-Duna; TAIPAI study group

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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.

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins


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