Association of HSD3B1 and HSD3B2 gene polymorphisms with essential hypertension, aldosterone level, and left ventricular structure

Abstract

Background: HSD3B1 and HSD3B2 are crucial enzymes for the synthesis of hormonal steroids, including aldosterone. Therefore, HSD3B gene variations could possibly influence blood pressure (BP) by affecting the aldosterone level. Methods: We performed a haplotype-and diplotype-based case-control study to investigate the association between the HSD3B gene variations and essential hypertension (EH), aldosterone level, and left ventricular hypertrophy (LVH). A total of 275 EH patients and 286 controls were genotyped for four SNPs of the HSD3B1 gene (rs3765945, rs3088283, rs6203, and rs1047303) and for two SNPs of the HSD3B2 gene (rs2854964 and rs1819698). Aldosterone and LVH were investigated in 240 and 110 subjects respectively. Results: Significant differences were noted for the total and the male subject groups for the recessive model (CC versus TCCTT) of rs6203 between the controls and EH patients (PZ0.030 and PZ0.008 respectively). The frequency of the T-C haplotype established by rs3088283-rs1047303 was significantly higher for EH patients compared with the controls (PZ0.014). Even though the polymorphism of HSB3B1 was not associated with LVH, the diplotype established by rs3088283-rs1047303 in the total subject group, along with the systolic BP, diastolic BP, and aldosterone level were significantly higher for those subjects who had the T-C haplotype versus those who did not (PZ0.025, PZ0.014, and PZ0.006 respectively). Conclusion: rs6203 and rs1047303 in the HSD3B1 gene are useful genetic markers for EH, while polymorphisms of HSD3B1 are associated with the BP and aldosterone level.

Association of the variations in the HSD3β gene with primary aldosteronism

“…In a Swedish population, rs6203 substitution of HSD3b1 contributed to the elevation of PAC and BP [8]. A similar observation of the HSD3b1 polymorphism was found in a Japanese cohort [9]. Subtype-specific expression of HSD3b1 and HSD3b2 in adrenal gland, observed by laser micro-dissection technique, demonstrated the expression of HSD3b1 in zona glomerulosa and HSD3b2 in zona fasciculata [7].…”

Hypertension Due to Loss of Clock: Novel Insight From the Molecular Analysis of Cry1/Cry2–Deleted Mice

“…Single nucleotide polymorphisms (SNPs) of human HSD3B1 were reported to contribute to the increase of systolic and diastolic BP [17] and PAC [18]. Together, these reports and our own finding suggest that HSD3B1, the orthologue of mouse Hsd3b6, is the rate-limiting factor for aldosterone synthesis in humans, may regulate PAC levels, and contributes to the regulation of BP.…”

Circadian Clock-Deficient Mice as a Tool for Exploring Disease Etiology

“…Human HSD3B1 may be a critical target for translational research. It has recently been shown that single-nucleotide polymorphisms (SNPs) of HSD3B1 are associated with elevated mean systolic and diastolic blood pressures 59) and PAC, 60) suggesting a functional contribution of HSD3B1 to aldosterone production within the human adrenal gland. It remains to be determined whether HSD3B1 is related to the pathogenesis of primary hyperaldosteronism and how sleep disorder and/or jet lag may perturb aldosterone biosynthesis and cause hypertension.…”