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

<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

<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

<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

OBJECTIVE: To analyze a child with 11β hydroxylase deficiency (11β-OHD) due to CYP11B2/CYP11B1 chimeric gene. METHODS: Clinical data of the child who was admitted to Henan Children's Hospital on August 24, 2020 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RT-PCR and Long-PCR were carried out to verify the presence of chimeric gene. RESULTS: The patient, a 5-year-old male, had featured premature development of secondary sex characteristics and accelerated growth, and was diagnosed with 21 hydroxylase deficiency (21-OHD). WES revealed that he has harbored a heterozygous c.1385T>C (p.L462P) variant of the CYP11B1 gene, in addition to a 37.02 kb deletion on 8q24.3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1385T>C (p.L462P) was rated as a likely pathogenic variant (PM2_Supporting+PP3_Moderate+PM3+PP4). The results of RT-PCR and Long-PCR suggested that CYP11B1 and CYP11B2 genes have recombined to form a CYP11B2 exon 1~7/CYP11B1 exon 7~9 chimeric gene. The patient was diagnosed as 11β-OHD and effectively treated with hydrocortisone and triptorelin. A healthy fetus was delivered following genetic counseling and prenatal diagnosis. CONCLUSION 11β-OHD may be misdiagnosed as 21-OHD due to the potential CYP11B2/CYP11B1 chimeric gene, which will require multiple methods for the detection.
Child, Preschool ; Humans ; Male ; Adrenal Hyperplasia, Congenital/genetics* ; Cytochrome P-450 CYP11B2/genetics* ; Exons ; Retrospective Studies ; Steroid 11-beta-Hydroxylase/genetics*

<p>OBJECTIVETo determine whether the blood pressure (BP) response to hydrochlorothiazide (HCTZ) was associated with the angiotensin converting-enzyme (ACE) I/D and aldosterone synthase (CYP11B2)-344T/C polymorphisms.p><p>METHODSThe BP response to HCTZ 12.5 mg once daily for 6 weeks was assessed in 829 subjects with mild or moderate essential hypertension, and compared across the ACE and CYP11B2 genotypes.p><p>RESULTSOf the 829 enrolled subjects, 785 completed the study. The systolic BP response differed according to the ACE (DD 9.4 +/- 15.7 mm Hg, ID 4.8 +/- 16.3 mm Hg, and II 5.1 +/- 14.8 mm Hg, P < 0.01), but not the CYP11B2 genotype (P > 0.05). Subjects with the combination of ACE DD and CYP11B2 CC genotypes tended to have a more pronounced systolic BP reduction than the other genotypic combinations of these 2 genes. Multiple linear regression analyses showed that the ACE DD genotype and serum aldosterone concentration at baseline were associated with the systolic BP reduction after treatment. None of the genetic associations with changes in diastolic BP or mean arterial pressure reached statistical significance (P > 0.05).p><p>CONCLUSIONSThe present study suggested that the ACE DD genotype was associated with the systolic BP response to HCTZ, and that the subjects with the combination of ACE DD and CYP11B2 CC genotypes might have a better BP response to HCTZ than the other genotypic combinations of these 2 genes.p>
Adult ; Aged ; Aged, 80 and over ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Single Nucleotide ; Sodium Chloride Symporter Inhibitors ; therapeutic use

<p>OBJECTIVETo explore the relationship between the -344T/C polymorphism of aldosterone synthase (CYP11B2) gene and essential hypertension in Chinese Mongolian population.p><p>METHODSBy cluster-sampling method, a total of 1575 Mongolian people in Tongliao city of Inner Mongolia were included in this study. And 417 subjects were normotension, 596 subjects were prehypertension and 562 subjects were essential hypertension. A survey was conducted to collect data by personal interview using a standard questionnaire, meanwhile fasting blood samples were drawn. Height, weight, waist circumference, blood pressure, blood-fat indexes and fasting plasma glucose were measured. The variant genotypes of CYP11B2 were identified by PCR assays. The relationship between the -344T/C polymorphism of CYP11B2 gene and essential hypertension were analyzed by multinomial logistic regression model.p><p>RESULTSCrude prevalence of prehypertension among Mongolian people was 37.84% (596/1575) and hypertension was 35.68% (562/1575). The age-standardized prevalence of prehypertension was 38.57% and hypertension was 31.53%. The frequency of the T and C allele was 0.66 (481/728) and 0.34 (247/728) for normotension group, 0.69 (696/1042) and 0.33 (346/1042) for prehypertension group, 0.71 (706/998) and 0.29 (292/998) for hypertension group. The multiple logistic models showed CYP11B2 variant genotypes were associated with prehypertension (TT/CC, OR = 1.33, 95%CI: 0.87 - 2.01; TC/CC, OR = 1.74, 95%CI: 1.13 - 2.67; TC + TT/CC, OR = 1.49, 95%CI: 1.01 - 2.22); CYP11B2 variant genotypes were associated with hypertension (TT/CC, OR = 1.70, 95%CI: 1.07 - 2.70; TC/CC, OR = 1.59, 95%CI: 0.98 - 2.50; TC + TT/CC, OR = 1.66, 95%CI: 1.06 - 2.58).p><p>CONCLUSIONCYP11B2 gene -344T/C polymorphism were associated with essential hypertension in Chinese Mongolian population.p>
Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Blood Pressure ; genetics ; China ; epidemiology ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Young Adult

<p>OBJECTIVETo investigate the association of the T(-344)C polymorphism of aldosterone synthase gene CYP11B2 with essential hypertension in Xinjiang Kazakh isolated population.p><p>METHODSThe study covered 186 hypertensives and 168 normotensive controls in Xinjiang Kazakh population. The segment of CYP11B2 was amplified from DNA by polymerase chain reaction(PCR). The PCR products were digested by restriction endonuclease.p><p>RESULTSThe frequencies of C and T in hypertensive group (0.45 and 0.55) were not significantly different from those in the control group (0.43 and 0.57; chi-square test=0.380, P=0.537). The frequencies of CYP11B2 genotypes of CC, CT and TT were 0.20, 0.50 and 0.30 in hypertensives respectively, and 0.12, 0.61 and 0.27 in controls respectively. There was no significant difference in genotypes between hypertensive group and normotensive group (chi-square test=4.838, P=0.089). But the frequencies of CC genotype were higher in the female hypertensives than in the normotensive controls (chi-square test=6.104, P<0.05).p><p>CONCLUSIONThe results suggested that the T(-344)C polymorphism of CYP11B2 gene may be associated with hypertension in female Kazakh population of Xinjiang Barlikun area.p>
Adult ; Asian Continental Ancestry Group ; Blood Pressure ; China ; ethnology ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Gene Frequency ; Humans ; Hypertension ; genetics ; physiopathology ; Male ; Middle Aged ; Polymorphism, Genetic ; Sex Factors ; Species Specificity

<p>OBJECTIVETo investigate the relationship of associating the polymorphisms of CYP11B2 -344C/T and Hind III restriction site on Y chromosome with essential hypertension.p><p>METHODSThis study enrolled 654 patients with essential hypertension and 386 healthy subjects as control group. The genomic DNA was extracted from blood leukocytes. The DNA segments of CYP11B2 and Y chromosome were amplified from genomic DNA by polymerase chain reaction (PCR). The PCR products were digested with Hae III or Hind III at 37 degrees centigrade respectively. The digested products were subjected to agarose gel electrophoresis and stain with ethidium bromide.p><p>RESULTS(1)The Hind III (-) genotype was found at 42.0% for patients with essential hypertension and 32.9% for control. The Hind III (-) genotype frequency of hypertension patient was significantly higher than that of the control (P was 0.03). The Hind III (+) genotype had a lower SBP and DBP than the Hind III (-) genotype (P was 0.01, P was 0.03). (2)With combining CC or CT genotype with Hind III (-) genotype, the relative risk suffering from hypertension was 1.998 fold high (P was 0.01).p><p>CONCLUSIONThe polymorphism of Hind III restriction site on Y chromosome is associated with essential hypertension, and when combined with polymorphism of CYP11B2 -344C/T, may have a united role to increase the risk of suffering from hypertension disease.p>
Adult ; Aged ; Alleles ; Binding Sites ; genetics ; Chromosomes, Human, Y ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Deoxyribonuclease HindIII ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics