It has been proven that familial aldosteronism type I is related to 11-beta hydroxylase (CYP11B1)/aldosterone synthase (CYP11B2) chimeric genes. In recent years, accumulated evidences indicate that the genetic basis of primary aldosteronism may involve chromosome 7p22 candidate genes, polymorphisms of CYP11B1 and CYP11B2 genes, mutations of ion channel- related KCNJ5, ATP1A1, CACNA1D genes. The article reviews the progress on genetic basis of primary aldosteronism.
Cytochrome P-450 CYP11B2 ; genetics ; Humans ; Hyperaldosteronism ; genetics ; Mutation ; Polymorphism, Genetic ; Steroid 11-beta-Hydroxylase ; genetics

The pathophysiological implications of aldosterone and adrenomedullin in the cardiac ventricular hypertrophy were examined. Male Sprague-Dawley rats were treated with deoxycorticosterone acetate (DOCA)-salt and monocrotaline (MCT) to selectively elicit left and right ventricular (LV, RV) hypertrophy, respectively. The mRNA expression of aldosterone synthase and adrenomedullin in LV and RV was determined by reverse transcription-polymerase chain reaction. The expression of aldosterone synthase and adrenomedullin was increased in LV, while not altered significantly in RV of DOCA-salt-treated rats. On the contrary, the expression was not significantly altered in LV, but increased in RV of MCT-treated rats. The enhanced expression of aldosterone synthase may be causally related with the development of ventricular hypertrophy, and the increased expression of adrenomedullin may act as a counter-regulatory mechanism.
Adrenomedullin* ; Aldosterone Synthase* ; Aldosterone* ; Animals ; Desoxycorticosterone ; Humans ; Hypertrophy ; Hypertrophy, Right Ventricular* ; Male ; Monocrotaline ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger

<p>OBJECTIVETo investigate the relationship between the aldosterone synthase (CYP11B2)-344C/T polymorphism and small artery compliance (C(2)).p><p>METHODSC(2) was measured by CVProfilor DO-2020 in 224 subjects, including 123 subjects with an abnormal C(2) and 101 normal controls. Genotypes of CYP11B2 were determined by polymerase chain reaction-based restriction fragment length polymorphism analysis.p><p>RESULTSThe frequencies of the CYP11B TT genotype and T allele in subjects with an abnormal C(2) were slightly higher than in normal controls, but the differences did not reach statistical significance (55.3% vs 41.6%, P > 0.05, 75.6% vs 66.8%, P > 0.05. However, when CT was combined with CC, the frequency of TT in subjects with an abnormal C(2) was significantly higher than in normal controls (P < 0.05). By CANOVA, TT subjects had a lower C(2) than CT and CC subjects (P < 0.05). Logistic regression analysis revealed that TT genotype was associated with abnormal C(2) (P = 0.043, OR = 1.93 95% CI 1.02-3.63).p><p>CONCLUSIONSThe CYP11B-344C/T polymorphism is associated with small artery compliance, and TT subjects are susceptible to abnormality of small arterial compliance.p>
Adult ; Arterioles ; physiology ; Cytochrome P-450 CYP11B2 ; genetics ; Elasticity ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVE: To analyze the clinical characteristics and genetic variants in a two-month-and-one-day male infant with aldosterone synthase deficiency. METHODS: Clinical data of the child was collected. Whole exome sequencing was carried out by next generation sequencing(NGS). Candidate variants were verified by Sanger sequencing. RESULTS: The infant had measured 54 cm (-2.1 SD) in length and 3.9 kg (-2.8 SD) in weight, and featured recurrent vomiting, poor feeding, apathetic appearance and failure to thrive. Blood electrolyte testing showed low sodium and increased potassium. Serum cortisol, adrenocorticotrophic hormone, 17-alpha-hydroxyl progesterone, androstenedione, and testosterone were all within the normal ranges. The plasma renin activity activity was increased, and plasma aldosterone level was low. NGS revealed that the infant has harbored compound heterozygous variants of the CYP11B2 gene, namely c.1334T>G(p.Phe445Cys) inherited from his father and c.1121G>A(p.Arg374Gln) inherited from his mother. Neither variant was reported previously, and both were predicted to be deleterious for the function of the protein product. CONCLUSION The compound heterozygous variants of c.1334T>G (p.Phe445Cys) and c.1121G>A (p.Arg374Gln) of the CYP11B2 gene probably underlay the disease in this patient.
Child ; Cytochrome P-450 CYP11B2/genetics* ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Mutation ; Whole Exome Sequencing

BACKGROUND: Evidence is accumulating that aldosterone secretion can be regulated in a paracrine and/or an autocrine manner by several neuropeptides locally released within the adrenal gland. Among neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) is present in high concentration in the human adrenal gland. The purpose of this study was to investigate the action of PACAP and the interaction between PACAP and angiotensin II (AII), the main physiologic aldosterone secretagogue, in aldosterone production in human H295R adrenocortical cells. METHODS: H295R cells were incubated with increasing concentrations of PACAP (10(-11)M~10(-7)M) in the absence or presence of 10(-7)M AII. Aldosterone concentration in the supernatant was determined by RIA. Intracellular cAMP content was measured by RIA and total inositol phosphate (IP) production by anion exchange chromatography. Gene expression of CYP11B2 was studied by RT-PCR. RESULTS: In H295R cells, PACAP stimulated aldosterone production in a dose-dependent manner. Incubation of H295R cells with PACAP in the presence of AII significantly increased aldosterone production, compared with that of PACAP alone. PACAP dose-dependently increased cAMP production, but 10(-7)M AII had no effect on either basal or PACAP-stimulated cAMP production. Total IP production was not affected by PACAP, but was increased by 10(-7)M AII; an increase that was not further increased by addition of PACAP. RT-PCR analysis of H295R cells which were exposed to 10-7M PACAP or 10(-7)M AII showed an increase in CYP11B2 transcript signal. Induction of CYP11B2 mRNA expression in response to treatment with both PACAP and AII was significantly more than that resulting from using PACAP alone. CONCLUSION: The present study demonstrates that PACAP exerts a direct stimulatory effect on aldosterone production through induction of CYP11B2 mRNA expression by adenylate cyclase activation as the main intracellular signal pathway in H295R cells. Furthermore, there may be some additive effects between PACAP and AII on aldosterone production.
Adenylyl Cyclases ; Adrenal Glands ; Aldosterone Synthase ; Aldosterone* ; Angiotensin II* ; Angiotensins* ; Chromatography ; Gene Expression ; Humans* ; Inositol ; Neuropeptides ; Pituitary Adenylate Cyclase-Activating Polypeptide* ; RNA, Messenger ; Signal Transduction

BACKGROUND AND OBJECTIVES: Several polymorphisms of the renin-angiotensin-aldosterone system have been found to have pleiotropic effects on cardiovascular diseases. Polymorphism of the aldosterone synthase gene (CYP11B2), which may influence plasma aldosterone levels, has been reported to cause systemic hypertension, influence the left ventricular diameter and mass, and decrease baroreflex sensitivity of the cardiovascular system. Through these mechanisms, it is thought to increase the risk of myocardial infarction (MI). Our study was designed to elucidate whether polymorphism of CYP11B2 increased the risk of MI. SUBJECTS AND METHODS: We analyzed the genotypes of CYP11B2 and the classic risk factors of MI in 188 MI patients and 320 control subjects without history of MI. RESULTS: There was no significant difference in the distribution of genotypes between the patient and control groups. Adjusting for the classical risk factors, multiple logistic regression analysis showed no significant effect of CYP11B2 gene polymorphism on the development of MI. However, the presence of the -344C allele is associated with a markedly increased MI risk conferred by classic risk factors including hypertension, smoking, and male sex. In particular, hypertension was not a significant risk factor as compared with non-hypertensive patients in subjects without -344C, but the relative risk was increased to 2.40 (95% CI:1.05-5.51, p<0.05) with - 344C. The relative risks of smoking and male sex were also increased with the presence of the - 344C allele. CONCLUSION: CYP11B2 polymorphism is not an independent risk factor of MI, although hypertension, smoking, and male sex are more potent risk factors for MI in Koreans who possess the - 344C allele.
Aldosterone Synthase* ; Aldosterone* ; Alleles ; Baroreflex ; Cardiovascular Diseases ; Cardiovascular System ; Genotype ; Humans ; Hypertension ; Logistic Models ; Male ; Myocardial Infarction* ; Plasma ; Polymorphism, Genetic ; Renin-Angiotensin System ; Risk Factors ; Smoke ; Smoking

Aldosterone synthase gene (CYP11B2) -344C/T polymorphism has been reported to be associated with serum aldosterone level, urinary aldosterone excretion, blood pressure, and left ventricular size and mass. The aim of this study was to evaluate the relation between CYP11B2 polymorphism and end-stage renal disease (ESRD) in the Korean population and the association with CYP11B2 polymorphism and cardiovascular morbidity in ESRD patients on hemodialysis. Genotyping was performed in 134 control subjects and 271 ESRD patients for CYP11B2 polymorphism using polymerase chain reaction through subsequent cleavage with restriction enzyme. Also current blood pressure, demographic, anthropometric and biochemical variables were investigated. The genotype distribution did not differ between ESRD patients and controls and there were no significant differences in blood pressure, use of antihypertensive medication, left ventricular hypertrophy and cardiovascular disease among the three genotypes in ESRD patients on hemodialysis. Our findings do not support the hypothesis that CYP11B2 polymorphism may be associated with prevalence of ESRD and suggest that CYP11B2 polymorphism may not be a genetic marker for cardiovascular morbidity in Korean ESRD patients.
Aldosterone ; Aldosterone Synthase ; Blood Pressure ; Cardiovascular Diseases ; Genetic Markers ; Genotype ; Humans ; Hypertrophy, Left Ventricular ; Kidney Failure, Chronic ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Prevalence ; Renal Dialysis

<p>OBJECTIVETo explore the association between CYP11B2 gene polymorphism and essential hypertension, blood pressure level in Chinese Han population by meta-analysis.p><p>METHODSAfter searching database, the research quality was quantified according to NOS. Genetic model, heterogeneity, publication bias, overall OR/standardized mean difference (SMD) and 95%CI were explored by Stata, 19 studies including 9249 subjects were included in this meta-analysis.p><p>RESULTSCompared to control group, OR(95%CI) of CC vs. TT, CT vs. TT, CC vs. CT in essential hypertensive patients were 1.022(95%CI: 0.879-1.190), 1.108 (95%CI: 0.951-1.291), 1.050(95%CI:0.995-1.109), respectively; SMD (95%CI) was 0.315 (0.066-0.565, P < 0.05) for systolic pressure derived CC vs. TT, and 0.088 (0.014-0.162, P < 0.05) for CT vs.p><p>TT CONCLUSIONIndividuals with -344C CYP11B2 allele are at higher risk of increased systolic blood pressure, but there is no evidence showing association between CYP11B2 polymorphism and susceptibility of essential hypertension in Chinese Han population.p>
Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Essential Hypertension ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; genetics ; Polymorphism, Single Nucleotide

<p>OBJECTIVETo explore the relationship between genetic polymorphisms of C-344T in the promoter region and K173R in the exon 3 of aldosterone synthase gene (CYP11B2) and the incidence of essential hypertension in a northern Chinese Han population.p><p>METHODSWe conducted a case-control study including 182 hypertensive patients and 189 healthy controls in Harbin newspaper office and assayed the genotypes of C-344T and K173R using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technology.p><p>RESULTSThe distributions of C-344T and K173R genotype frequencies in men and women were in accordance with the Hardy-Weinberg equilibrium. The differences of C-344T allele and genotype as well as K173R allele frequency distributions between hypertensive patients and healthy controls were not statistically significant in men and women and pooled population (P > or = 0.05). The difference of K173R genotype frequency distribution reached borderline significance (P = 0.0500) and was more pronounced in women (P = 0.0038) according to the dominant mode of inheritance. Moreover, the magnitude of this mode of inheritance was more remarkable after the confounding factors were adjusted. K173R statistically correlated with the systolic hypertension in women.p><p>CONCLUSIONThe CYP11B2 K173R polymorphism correlates with the susceptibility of essential hypertension in the northern Chinese Han population.p>
Asian Continental Ancestry Group ; Case-Control Studies ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Hypertension ; genetics ; Male ; Polymorphism, Genetic

<p>OBJECTIVETo investigate whether the -344T/C polymorphism of CYP11B2 gene is associated with essential hypertension in the Hans in Shandong province.p><p>METHODSPlasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured with radioimmunoassays; the hypertensives were classified as low-renin and normal- or high-renin group by PAC/PRA ratio. -344T/C polymorphism was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) in controls and hypertensives.p><p>RESULTSNo significant differences were found in genotype distribution or allele frequency between groups of control and primary hypertension or between groups of control and normal- or high-renin hypertension. The C allele frequency in low-renin hypertension group was significantly higher than that in normotensives and normal- or high-renin hypertension group (P < 0.05).p><p>CONCLUSIONThese results suggest that -344T/C polymorphism of CYP11B2 gene may be associated with low-renin essential hypertension in the Han nationality in Shandong province.p>
Asian Continental Ancestry Group ; genetics ; China ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Humans ; Hypertension ; ethnology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide