Polymorphisms in CYP11B2 and CYP11B1 genes associated with primary hyperaldosteronism

Abstract

Several frequent polymorphisms in the CYP11B2 gene are suggested to be associated with essential hypertension and aldosterone secretion. In this study, we investigated the association of polymorphisms in CYP11B2 and CYP11B1 genes with the risk of primary hyperaldosteronism (PH). Three polymorphisms in the CYP11B2 gene (intron 2 conversion, rs1799998 and rs4539) and two polymorphisms in the CYP11B1 gene (rs6410 and rs6387) were analyzed in patients with PH and in the normal population. The rs6410 allelic frequencies in patients with aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were significantly different from those in controls at P¼1.09Â10 À5 and 0.015, respectively. There was a relative excess of AA homozygotes and AG heterozygotes of the rs6410 allele in the APA group as compared with the control group (P¼2.19Â10 À4 ). There were significantly different genotypes, AA and AG, of the rs6410 allele between the patients with IHA and the controls only after adjustments for age, gender and body mass index (odds ratio (OR)¼4.06, 95% confidence interval (CI) 1.31-12.66; OR¼2.41, 95% CI 1.02-5.72). One susceptible haplotype, AAAWT, was identified to be significantly associated with APA (OR¼1.44, 95% CI 1.19-1.76), and three susceptible haplotypes, AAAWT, AGGWT and AGAWC, were identified to be significantly associated with IHA (OR¼1.55, 95% CI 1.23-1.96; OR¼1.49, 95% CI 1.17-1.89; OR¼1.40, 95% CI 1.04-1.88). In contrast, one protective haplotype, GGAWT, showed a significant difference between the patients with APA and controls (OR¼0.73, 95% CI 0.55-0.97). Several haplotypes were associated with ARR in both the controls and cases. Our data demonstrated that there was a significant association between polymorphisms in the CYP11B2 and CYP11B1 genes and a genetic predisposition to PH. The association with IHA seemed closer compared with APA.

Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke

“…New therapeutic options suggested by our study for control of blood pressure include the genes Calcrl , Cyp11b1 and Prcp [36]. CALCRL (calcitonin receptor-like) is a multifunctional vasodilator peptide that was persistently upregulated in aged rats whereas Cyp11b1 is associated with essential hypertension and had decreased levels in both age groups [37]. Activity modulators available for all three of these genes [38]–[40].…”

Aldosterone Synthase Promoter Polymorphism and Cardiovascular Phenotypes in a Large, Multiethnic Population-Based Study

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Aldosterone production has been reported to associate with variation at this locus [À344C/T, rs1799998]. 1 Moreover, clinically overt phenotypes that may be mediated by aldosterone have been linked to this SNP.…”

Association Between the Polymorphism of Steroid Hormone Metabolism Genes and High-Altitude Pulmonary Edema in the Chinese Han Population

“… 39 It has been reported that there is a significant association between polymorphisms in CYP11B2 and CYP11B1 and a genetic predisposition towards primary hyperaldosteronism. 40 …”

“…39 It has been reported that there is a significant association between polymorphisms in CYP11B2 and CYP11B1 and a genetic predisposition towards primary hyperaldosteronism. 40 Several studies have reported that some genetic loci associated with lung-related diseases overlap with loci for pulmonary fibrosis. [41][42][43] For example, two chronic obstructive pulmonary disease-associated loci (FAM13A and DSP) overlap with loci for lung function and pulmonary fibrosis, 42 while five pulmonary fibrosis-associated loci (DPP9, DSP, FAM13A, IVD, and MUC5B) are also significantly associated with interstitial lung abnormalities.…”