CYP11B2 Gene Polymorphism Research Articles

Анализ частоты встречаемости полиморфизмов генов CYP2C9, AGTR1, AGT, ACE, CYP11B2 у пациентов с впервые выявленной артериальной гипертензией 1–2 степеней

Анализ частоты встречаемости полиморфизмов генов CYP2C9, AGTR1, AGT, ACE, CYP11B2 у пациентов с впервые выявленной артериальной гипертензией 1–2 степеней

Effects of CYP11B2 gene polymorphisms on adrenocorticotropic hormone and angiotensin II in type 2 diabetes patients with hypertension

The aim of this study is to investigate the effects of CYP11B2 gene polymorphisms with the adrenocorticotropic hormone (ACTH) and angiotensin II (Ang II) in Chinese patients with type 2 diabetes (T2DM) and hypertension (T2MH). A total of 457 T2DM patients were genotyped for the polymorphism of rs3802228 and rs1799998 using SNP-scan high-throughput technology. The levels of adrenocorticotropic hormone in peripheral blood and related biochemical indices including aldosterone, renin, and Angiotensin II were measured and analyzed in relation to CYP11B2 polymorphisms in T2DM patients. As we found that Compared with T2DM patients, ACTH levels were higher in the rs3802228 AA/AG and rs1799998 AA/AG genotype T2MH subgroups (P < 0.001, P = 0.001). However, the difference in ACTH levels between two identical genotypes of T2MH was not statistically significant compared with T2DM patients (P > 0.05), whereas both AA and AG genotype subgroups had different AngII levels (P < 0.001, P = 0.004), which were higher than those of T2DM patients, but with a decrease in ACTH levels compared with patients with a single AA or AG genotype. Logistic regression analyses indicated that there was no significant relationship between genotype and allele polymorphisms with T2MH progression after adjustment for confounders. As a conclusion, CYP11B2 gene polymorphism was not associated with susceptibility to hypertension in Chinese T2DM patients, but its association with ACTH and Ang II levels may be a risk factor for susceptibility to hypertension in Chinese T2DM patients.

ROLE OF THE T (-344) C POLYMORPHISM OF ALDOSTERONE SYNTHASE GENE CYP11B2 IN THE DEVELOPMENT OF CARDIORENAL SYNDROME IN PATIENTS WITH DIABETES MELLITUS

Objective: To evaluate the role of the T (-344)C polymorphism of CYP11B2 gene in the development of cardiorenal syndrome (CRS) in diabetes mellitus (DM). Design and method: We examined 270 patients with type 1 and type 2 diabetes aged over 25 years. Control group included 60 healthy patients the same age. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio. All patients underwent molecular genetic analysis using deoxyribonucleic acid isolated from whole venous blood. Results: The frequency of carriage of the TT polymorphism of the CYP11B2 gene was significantly higher (47%) in the group of patients with DM than in the control group (26%). Carriers of the TT genotype had significantly high levels of homocysteine (10.5 [8.3;15.1] μmol/L) and FGF-23 (3.22 [0.77;7.60] pmol/L) as in DM group and in the control group (8.3 [7.54;10.9] μmol/l and 2.4 [2.19;2.6] pmol/l, respectively) than carriers of the CC genotype. The TT genotype was associated with the risk of developing CRS manifestations such as left ventricular hypertrophy (odds ratio (OR) 2.64; 95% CI (0.93–4.19), chronic heart failure (OR 4.26; 95% CI (2.26 - 8.06), subclinical atherosclerosis (OR 4.04; 95% CI (1.89 - 8.58), chronic kidney disease (CKD) (OR 10.77; 95% CI (3.56 - 32.61), and the CT genotype (OR 3.28; 95% CI (1.02 – 10.59) with CKD risk. Conclusions: There are pathogenetic association between the renin-angiotensin-aldosterone system, cardiovascular complications and a decrease renal function. Further research is needed for a deep understanding of the complex pathogenetic mechanisms of the development and progression of cardiovascular and renal pathology.

Association between Aldosterone Synthase (CYP11B2) Gene Polymorphism and Hypertension in Pashtun Ethnic Population of Khyber Pakhtunkwha, Pakistan.

Genome-wide association studies significantly increased the number of hypertension risk variants; however, most of them focused on European societies. There is lack of such studies in developing countries, including Pakistan. The lack of research studies and the high prevalence of hypertension in the Pakistani community prompted us to design this study. Aldosterone synthase (CYP11B2) was thoroughly studied in different ethnic groups; however, no such study has been conducted in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. In essential hypertension, the aldosterone synthase gene (CYP11B2) plays a significant role. Aldosterone synthesis is affected by both hereditary and environmental factors. Aldosterone synthase (encoded by the CYP11B2 gene) controls the conversion of deoxycorticosterone to aldosterone and, thus, has genetic influences. Polymorphisms in the CYP11B2 gene are linked to an increased risk of hypertension. Previous research on the polymorphism of the aldosterone synthase (CYP11B2) gene and its relationship to hypertension produced inconclusive results. The present study investigates the relationship between CYP11B2 gene polymorphism and hypertension in Pakistan's Pashtun population. We used the nascent exome sequencing method to identify variants associated with hypertension. The research was divided into two phases. In phase one, DNA samples from 200 adult hypertension patients (of age ≥ 30 years) and 200 controls were pooled (n = 200/pool) and subjected to Exome Sequencing. In the second phase, the WES reported SNPs were genotyped using the Mass ARRAY technique to verify and confirm the association between WES-identified SNPs and hypertension. WES identified a total of eight genetic variants in the CYP11B2 gene. The chi-square test and logistic regression analysis were used to estimate the minor allele frequencies (MAFs) and chosen SNPs relationships with hypertension. The frequency of minor allele T was found to be higher in cases compared to the control (42% vs. 30%: p = 0.001) for rs1799998 of CYP11B2 gene, while no significant results (p > 0.05) were observed for the remaining SNPs; rs4536, rs4537, rs4545, rs4543, rs4539, rs4546 and rs6418 showed no positive association with HTN in the studied population (all p > 0.05). Our study findings suggest that rs1799998 increases susceptibly to HTN in the Pashtun population of KP, Pakistan.

Clinical significance of the T(-344)C polymorphism of the aldosterone synthase gene (CYP11B2) in the prognosis of cardiorenal syndrome in diabetes mellitus

Objective. To evaluate the role of the T(-344)C polymorphism of CYP11B2 gene in the development of cardiorenal syndrome (CRS) in diabetes mellitus (DM).Materials and methods. 270 patients with type 1 and type 2 diabetes aged over 25 years were examined. All patients underwent molecular genetic analysis using deoxyribonucleic acid isolated from whole venous blood.Results. The TT genotype was associated with the risk of developing CRS manifestations such as left ventricular hypertrophy (odds ratio (OR) 2.64; 95% CI (0.93–4.19), chronic heart failure (OR 4.26; 95% CI (2.26 - 8.06), subclinical atherosclerosis (OR 4.04; 95% CI (1.89 - 8.58), chronic kidney disease (CKD) (OR 10.77; 95% CI (3.56 - 32.61), and the CT genotype (OR 3.28; 95% CI (1.02 – 10.59) with CKD risk..Conclusion. There are pathogenetic associations between renin-angiotensin-aldosterone system, cardiovascular complications and a decrease of renal function. Further research is needed for a deep understanding of the complex pathogenetic mechanisms of the development and progression of cardiovascular and renal pathology.

DEPENDENCE OF METABOLIC DISORDERS ON ALDOSTERONE SYNTHASE CYP11B2 (-344C/T) GENE POLYMORPHISM IN HYPERTENSIVE PATIENTS

Objective: The aim of the study was to analyze the association of CYP11B2 (-344C/T) gene polymorphism with lipids profile and aldosterone level changes in patients with essential arterial hypertension (EAH). Design and method: One-hundred subjects with EAH and target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Among them 79.0% females and 21.0% males, mean age 59.87 ± 8.02; disease duration from 6 to 25 years. Control group included 48 practically healthy persons of relevant age. Gene polymorphism of aldosterone synthase gene CYP11B2 (-344C/T) was examined by polymerase chain reaction. Lipids’ profile in serum was studied by total cholesterol (TC), high- and low density levels cholesterol (HDL-C, LDL-C), triglycerides (TG) concentration and atherogenic index (AI). Aldosterone plasma concentration was assessed by ELISA. Results: The TG level and atherogenic index were higher in T-allele carriers than in CC-genotype of CYP11B2 gene: in patients by 22.61–56.2% (p &lt; 0.05), in control group by 31.16–77.42% (p &lt; 0.05). Contrary, the HDL-C level was lower T-allele carriers in both groups: by 12.23% and 12.95% (p &lt; 0.05) in patients and by 18.34% and 27.22% (p &lt; 0.05) in control group, respectively. Significant differences in lipids profile data between patients and control groups depending on genotypes were not observed. Aldosterone concentration elevated also in T-allele carrier’s patients by 53.62% (p &lt; 0.001) and 26.90% (p = 0.015), than in CC-genotype and was 2.14–2.72 times higher, than in control group (p &lt; 0.001). TG level in CC-genotype males was higher, than in CC-genotype’s women by 68.57% (p = 0.028), but in TT-genotype males HDL-C was reliably lower by 18.40% (p = 0.008) than in TT-carriers’ women with higher atherogenic index by 25.84% (p = 0.031). Otherwise, aldosterone concentration was certainly higher in women, than in men regardless the genotypes of CYP11B2 gene. But aldosterone level prevailed in T-allele carriers of both genders over CC-genotype patients’ data: by 27.01% and 49.64% (p &lt; 0.05) for women and by 20.93% and 43.11% (p &lt; 0.05) for men. Conclusions: Thus, TT-genotype or T-allele of aldosterone synthase gene CYP11B2 (-344C/T) associated with higher blood level of triglycerides and aldosterone concentration (especially in females), elevated atherogenic index and lower HDL-C rate (preferably in males).

Contribution of polymorphism of genes of aldosterone synthetase CYP11B2 (C-344T), adrenergic receptors type 1 ADRB1 (Gly389Arg) and type 2 ADRB2 (Arg16Gly) to formation of different obesity phenotypes

Objective. To study the relationship of polymorphism of the genes of aldosterone synthetase CYP11B2 (C-344T), adrenergic receptor type 1 ADRB1 (Gly389Arg) and type 2 ADRB2 (Arg16Gly) with the risk of obesity.&#x0D; Materials and methods. The study involved 170 patients; the mean age was 45.4 7.3 years. The patients were divided into 2 groups: group 1 obese patients with metabolic disorders in combination with 1-2 degree hypertension complicated obesity (n = 90); group 2 50 participants with obesity without metabolic disorders (metabolically healthy obesity). The control group consisted of 100 healthy respondents. All the surveyed persons underwent anthropometry and general clinical studies according to the recommendation for examination of patients with obesity and arterial hypertension. Total DNA was isolated from venous whole blood samples by RT-PCR using the DNA-Sorb-B kit. &#x0D; Results. It was found that in the group of complicated obesity, the carriage of the TT genotype of the CYP11B2 gene polymorphism (C-344T) and the CG genotype of the Gly389Arg polymorphism of the ADRB1 gene prevailed in comparison with the group of metabolically healthy obesity and healthy respondents. The predominance of carriage of the GG genotype of the ADRB2 gene polymorphism (Arg16Gly) was revealed in the groups of metabolically healthy obesity and complicated obesity in comparison with the healthy group. An association of the polymorphic position of the ADRB1 (Gly389Arg) and ADRB2 (Arg16Gly) genes with the level of low-density lipoprotein cholesterol, triglycerides, the level of systolic blood pressure and diastolic blood pressure, and the level of uric acid was established. The relationship between the polymorphism of the CYP11B2 (C-344T) promoter region and the level of glomerular filtration rate and total cholesterol was determined.&#x0D; Conclusions. Analysis of ADRB1 (Gly389Arg), ADRB2 (Arg16Gly), and CYP11B2 (C-344T) gene polymorphism variants can be used as an additional marker to assess the risk of developing obesity, arterial hypertension, and metabolic disorders.

Effect of ACE, ACE2 and CYP11B2 gene polymorphisms and noise on essential hypertension among steelworkers in China: a case\u2013control study

BackgroundPrevious studies on the relationship between ACE I/D, ACE2 G8790A and CYP11B2-344T/C gene polymorphisms and essential hypertension (EH) were inconsistent. Moreover, few studies have reported the combined effect of these gene polymorphisms and noise exposure on EH. The purpose of this study was to explore the combined and separate effects of ACE I/D, ACE2 G8790A and CYP11B2-344T/C gene polymorphisms and noise on EH among steelworkers.MethodsA case–control study was conducted on 725 male workers between March 2014 and July 2014 in the Tangsteel Company, China. The noise exposure of the workers were measured. Logistic regression and crossover analysis were used to analyse the effects of the interactions on the EH among steelworkers. GMDR was used to determine the best combination model of gene–noise interactions.ResultsMultivariate logistic regression showed that noise exposure increased the odds of EH, and the OR is 1.52 (95% CI 1.04–2.22). The risk of having EH for ACE I/D DD genotype carriers was 1.99 times that for II genotype carriers (95% CI 1.14–3.51). There was a negative additive interaction between ACE2 G8790A and CYP11B2-344T/C on EH (U3 = − 2.221, P = 0.026, and S = 0.128) and a positive multiplicative interaction between ACE I/D and CYP11B2-344T/C on essential hypertension (P = 0.041). In addition, there was no significant gene–noise interaction model through the GMDR method after adjusting the confounders.ConclusionsThe ACE DD genotype may make men susceptible to EH. Simultaneously carrying the DD genotype of ACE I/D and the TC genotype of CYP11B2-344T/C increased the risk of EH.

Contribution of the ACE (rs1799752) and CYP11B2 (rs1799998) Gene Polymorphisms to Atrial Fibrillation in the Tunisian Population.

This study investigated the association of angiotensin-converting enzyme (ACE I/D) and aldosterone synthase (CYP11B2-344C/T) gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) with atrial fibrillation (AF) in the Tunisian population. The study population included 120 patients with AF and 123 age-matched controls. Genotyping of the I/D polymorphism in the ACE gene and the -344C/T polymorphism in the CYP11B2 gene was performed by polymerase chain reaction (PCR) and PCR-RFLP methods, respectively. The genotype distribution of the ACE I/D and CYP11B2-344C/T polymorphisms was significantly different between AF patients and control participants (p < 0.01 and p < 0.006 respectively). In addition, ACE I/D increased the risk of AF significantly by 3.41-fold for the DD genotype (OR = 3.41; 95% CI [1.39-8.34]; p < 0.007), and after adjusting for confounding factors (age, diabetes, hypertension, and dyslipidemia), the risk was higher (OR = 5.71; 95% CI [1.48-21.98]; p < 0.01). Likewise, the CYP11B2-344C/T polymorphism increased the incidence of AF for the TT genotype (OR = 3.66; 95% CI [1.62-8.27]; p < 0.002) and the CT genotype (OR = 2.68; 95% CI [1.22-5.86]; p < 0.01). After adjusting for confounding factors (age, diabetes, hypertension and dyslipidemia), the risk remained higher for the TT genotype (OR = 3.58; 95% CI [1.08-11.77]; p < 0.03). Furthermore, the haplotype-based association of the ACE I/D and CYP11B2-344C/T polymorphisms showed that the D-T haplotype increased the risk for AF. Our study suggests a significant association of the ACE (I/D) and CYP11B2-344C/T polymorphisms with AF in the Tunisian population.

Correlations of CYP11B2 gene polymorphisms with eclampsia.

The aim of this study was to explore the relationship between CYP11B2 gene polymorphisms and eclampsia. A total of 400 pregnant women treated in our hospital were enrolled in this study, including 200 normal pregnant women (pregnancy group) and 200 pregnant women with eclampsia (eclampsia group). Peripheral blood was collected from subjects of the two groups. Subsequently, genomic deoxyribonucleic acids (DNAs) were extracted and amplified via polymerase chain reaction (PCR) for detection of CYP11B2 rs4543, rs3802228 and rs104894072 polymorphisms. The expression level of CYP11B2 gene was measured as well. Additionally, the correlations of CYP11B2 gene polymorphisms with blood pressure and coagulation and renal function indexes were analyzed. The distribution of alleles of rs4543 locus in CYP11B2 gene was significantly different between eclampsia group and pregnancy group (p=0.027). The frequency of the allele C was significantly lower in eclampsia group than that of pregnancy group (p<0.05). There was a statistically significant difference in the genotype distribution of CYP11B2 rs3802228 (p=0.000) and rs104894072 (p=0.000) between eclampsia group and pregnancy group (p<0.05). Meanwhile, the frequency of AA genotype of rs3802228 and TG genotype of rs104894072 was remarkably higher in eclampsia group than that in pregnancy group (p<0.05). The distribution of the locus rs104894072 (p=0.044) in dominant model and rs3802228 (p=0.002) in recessive model in eclampsia group was different from that in pregnancy group (p<0.05). Eclampsia group showed remarkably elevated frequency of TT + TG of the locus rs104894072 in dominant model and lowered frequency of AG + GG of the locus rs3802228 in recessive model (p<0.05). Similarly, a significant difference was observed in the distribution of the haplotypes CGG (p=0.001) and TGT (p=0.048) in CYP11B2 gene between eclampsia group and pregnancy group (p<0.05). The linkage disequilibrium of the loci rs3802228 and rs104894072 was relatively high (D'=0.382). The polymorphism of the locus rs104894072 in CYP11B2 gene had an evident relation to CYP11B2 gene expression (p<0.05). Meanwhile, the expression of CYP11B2 gene was markedly higher in patients with GG genotype in eclampsia group (p<0.05). The polymorphism of CYP11B2 rs4543 was notably associated with PT level of patients in eclampsia group (p=0.000). Conversely, rs3802228 polymorphism was correlated with 24 h urine protein level (p=0.000). Besides, the proportion of patients with CGG haplotype was significantly larger among patients with systolic blood pressure of 140-160 mmHg (p<0.05). In addition, the proportion of patients with TGT haplotype was evidently greater among patients with systolic blood pressure >180 mmHg in eclampsia group (p<0.05). CYP11B2 gene polymorphisms are significantly correlated with the development and progression of eclampsia.

Relationship of gene polymorphism with the nature of target organ damage in patients with arterial hypertension

Objective: to assess the relationship of polymorphism of the main genes involved in the pathogenesis of arterial hypertension (AH) with indicators reflecting the state of target organs in the group of patients with arterial hypertension.Material and methods: we examined 100 patients with arterial hypertension who underwent standard diagnostic procedures, as well as molecular genetic research.Results: in patients with arterial hypertension statistically significant associations of AGTR2, GNB3, and NOS3 gene polymorphism with left ventricular hypertrophy, CYP11B2 and NOS3 gene polymorphism with left ventricular diastolic dysfunction, and NOS3 gene polymorphism with increased vascular wall stiffness were found (p &lt; 0.05).Conclusions: the results of the study indicate that patients with arterial hypertension are a genetically heterogeneous group in terms of the relationship of specific gene polymorphism with indicators that characterize the state of target organs. The use of genetic approaches is promising for early screening of patients with arterial hypertension, belonging to the high-risk group, in order to ensure timely and effective organoprotection.

Contribution of rs1799998 polymorphism in CYP11B2 gene in susceptibility to preeclampsia

Abstract Objectives: the present study aimed to evaluate the association between the rs1799998 polymorphism of the CYP11B2 gene and the susceptibility to preeclampsia (PE) in a Brazilian population. Methods: the study group comprised 61 women who were diagnosed with PE. The control group included 116 women who did not show changes in their blood pressure levels during their pregnancies. The rs1799998 polymorphism of the CYP11B2 gene was amplified by allele-specific polymerase chain reaction (PCR). A multiple logistic regression analysis was performed using the SNPStat program to evaluate the risk of the CYP11B2 gene rs1799998 polymorphism contributing to PE. Results: the PE group had the following genotypes: 1.64% CC, 91.80% CT, and 6.56% TT. In the control group, the observed genotypic frequencies were: 11% CC, 73% CT, and 16% TT. The genotypic frequency distribution did not fit the Hardy Weinberg Equilibrium (HWE) in either study group. The multiple logistic regression analysis showed a statistically significant difference for the rs1799998 polymorphism in the recessive model. Conclusion: the results suggest an association between the recessive model of C/C genotype of the rs1799998 polymorphism of the CYP11B2 gene and susceptibility to PE.

Association of CYP11B2 gene polymorphism with preeclampsia in north east of Iran (Khorasan province)

PurposeIdentification the genetic factors in preeclampsia (PE) are useful to increase the current knowledge of the pathophysiology of the disorder. The genetic factors implicated for all cases of PE remain to be determined. This study was aimed to investigate association between ADD1 1378G > T, AGTR2 1675G > A, AGTR1 1166A > C, NOS3 894 G > T and CYP11B2 −344C > T gene polymorphisms in Iranian women with PE. Material and Methods117 pregnant women with PE and 103 healthy women without affected previous pregnancy by PE were selected. Genomic DNA was extracted from peripheral blood and real-time PCR was performed to investigate the polymorphisms using a commercial kit. ResultsThere was a significant difference in CYP11B2 −344C > T gene polymorphism between case and control groups (P = 0.025). The odds ratio was 0.71 (CI 95% = 0.28–1.79). There were no statistical significant differences between other genetic polymorphisms. ConclusionOur results showed a significant association between CYP11B2 −344C > T gene polymorphism with PE. This finding suggests that mentioned polymorphism may be associated with susceptibility to PE at least in IRAN.

The inappropriateness of left ventricular mass and echoreflectivity in males with essential hypertension and different CYP11B2 gene polymorphisms

Background. The CYP11B2 gene as the main controller of aldosterone plasma activity is likely to be responsible as for the BP level as for the expression of different traits of hypertensive cardiac remodeling such as increased left ventricular mass and myocardial fibrosis. The main objective of our study was to define the differences in myocardial remodeling depending on CYP11B2 gene polymorphism. It was shown that some special techniques of echocardiography such as the assessment of inappropriate left ventricular mass and myocardial echoreflectivity proved additional information in patients with hypertensive heart disease. That’s why these techniques were used for a more precise assessment of hypertensive cardiac remodeling. Material and methods. Our study involved 150 males aged 45–60 years. They were divided into three groups: Group 1–50 patients with normal BP without any echocardiographic abnormalities, Group 2–52 patients with essential hypertension without left ventricular hypertrophy, and Group 3–48 patients with essential hypertension and left ventricular hypertrophy. Results. It was found that in patients with inappropriate LVM the prevalence of CC genotype was almost twice higher than among those with appropriate LVM. On the other hand, hypertensive patients with CC genotype and LVH demonstrated higher echoreflectivity parameters. Conclusions. We assume that CC polymorphism of CYP11B2 may be an indicator of more expressed signs of hypertensive cardiac remodeling, in particular myocardial hypertrophy and myocardial fibrosis, in males with essential hypertension.

Brain natriuretic peptide in the diagnosis of structural and functional changes of the myocardium in men with uncomplicated and asymptomatic hypertension with polymorphic variants of aldosteronesynthase gene

According to previous studies, aldosterone is responsible for myocardial remodeling and, ultimately, myocardial dysfunction. Aldosterone synthase gene (CYP11B2) as the main controller of aldosterone may be involved in the variability of renin-angiotensin-aldosterone system (RAAS) activity. Brain natriuretic peptide (BNP) is a marker for the diagnosis of chronic heart failure and it’s a contraregulatory peptide of RAAS. The aim of our study was to investigate the levels of BNP plasma concentrations in men with uncomplicated hypertension, carriers of polymorphic variants of the CYP11B2 gene. The study involved 150 men: 50 men of control group and 100 men of main group patients with hypertension of I-II stages. Each participant underwent office blood pressure measurement, echocardiography, determination of plasma levels of BNP in serum by immunoassay (ELISA) and determination of C-344T polymorphism of CYP11B2 gene in venous blood samples by PCR. Mathematical processing of obtained data was performed using standard statistical package STATISTICA 10.0. In accordance with the normal distribution, obtained results were presented as mean and standard deviation. In case of discrepancy of normal distribution a median of 25-75% of quartiles, including half of all parameter values, was given. For comparing groups by investigated parameters, the Student's t test was used for normal distribution, and in the absence of normal distribution, its non-parametric analogs were used: the Mann-Whitney or ANOVA test. It was found that male carriers of CC polymorphism of CYP11B2 gene had higher plasma concentrations of BNP and in the group of patients with essential hypertension and left ventricle hypertrophy (LVH) the representatives of this polymorphic variant of CYP11B2 gene had more severe diastolic disorders and signs of myocardial remodeling. The TT carrier of the CYP11B2 gene polymorphism was associated with excess body mass and lower BNP levels.

Significance of aldosterone synthase gene (CYP11B2) polymorphism as a component of the renin-angiotensin-aldosterone system in the pathogenesis of myocardial hypertrophy in hypertension: literature review and own experience

Aldosterone synthase gene is one of the candidate genes responsible for the effects of aldosterone. In particular, there are some evidences concerning the influence of this gene on the myocardial remodeling in hypertension. The analysis and summary of the results of published researches devoted to the study of aldosterone synthase gene (CYP11B2) polymorphism and its importance in the processes of hypertensive myocardial remodeling are presented in the article. Pub Med and EMBASE databases were used. The results of the study of CYP11B2 polymorphism within the framework of the research work at the Department of Internal Medicine of Medical Faculty №2 are presented in the article. The aim of the study is to study the importance of polymorphism of aldosterone synthase gene in the pathogenesis and clinic of hypertension. It has been shown that among both, hypertensive and males, residents of Podillia region of Ukraine, the overwhelming majority were carriers of TC polymorphism of CYP11B2 gene. These data are in the agreement with the previous studies in the European population.

Association of aldosterone synthase CYP11B2 (-344C/T) gene polymorphism with essential hypertension and left ventricular hypertrophy in the Egyptian population

ABSTRACTBackground and Objectives: Essential hypertension is a complex progressive cardiovascular disorder. Renin–angiotensin aldosterone system (RAAS) plays a major role in blood pressure regulation. Aldosterone, synthesized in the adrenal cortex by aldosterone synthase is encoded by the CYP11B2 gene. This case-control study was aiming to investigate the relationship between the aldosterone synthase gene (CYP11B2) biallelic polymorphism in the promoter at position −344 (−344C/T) with essential hypertension and left ventricular hypertrophy in the Egyptian population.Methods: This study was conducted on 100 hypertensive patients (group I) and 50 healthy control subjects (group II). Serum aldosterone, plasma renin, ARR levels were investigated. Echocardiography was done to evaluate LV dimensions. Genotyping of the CYP11B2 gene was performed by PCR/RFLP confirmed by direct sequencing.Results: Our study revealed that CYP11B2 (−344T) allele was significantly higher than (−344C) allele in hypertensive patients as compared to healthy control (OR-2.51; 95% CI:1.3–3.5; P = 0.002) and −344TT genotype was associated with increased LVMI as compared with −344CC genotype (P = 0.001).Conclusion: A Significant association was observed between the CYP11B2 (−344C/T) polymorphism and −344T allele and essential hypertension in the Egyptian population. Also, we found that the CYP11B2 −344C/T polymorphism and −344T allele are associated with left ventricular hypertrophy which may predispose to cardiovascular complications of hypertension.

Genetically determined enlargement of carotid body evaluated using computed angiotomography

It has recently been established that carotid bodies play a significant role in the regulation of activities of the cardiovascular system as well as in the pathogenesis of arterial hypertension, heart failure and diabetes. Aim of study was to determinate the influence of polymorphisms within genes of the renin-angiotensin-aldosterone system (RAAS) on the volume of the carotid bodies (CB) in patients with hypertension (HTA).The study group consisted of 77 patients with HTA. All patients were genotyped for single-nucleotide polymorphisms of genes coding for: angiotensinogen: rs4762, rs5049, rs5051 and rs699; angiotensin-converting enzyme: rs4343; angiotensin receptor type 1 gene (AGTR1): rs5182 and rs5186; and the aldosterone synthase: rs1799998. The estimation of volumes of CB (VrCB+lCB) was based on computed tomography angiography.Among individuals with essential hypertension certain relationships were documented between rs5182 and rs5186 polymorphisms of AGTR1 gene and rs1799998 polymorphism of CYP11B2 gene on one hand and the volume of carotid bodies on one other. Patients carrying the C alleles within the rs5182 and rs5186 of AGTR1 gene was associated with higher values of VrCB+lCB. The carriage of the T allele in the rs5182 locus of the AGTR1 gene determine lower values of VrCB+lCB.In summary, in patients with HTA a higher volume of CB may be resulted from the presence of specific genotypes in RAAS.

The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients.

Longevity of peritoneal membrane is an important issue in patients treated with peritoneal dialysis (PD). In our study, we studied the impact of angiotensin receptor 1 (AGT R1) and aldosterone synthase (CYP11B2) gene polymorphism on peritoneal concentrations of interleukin-6 (PI-IL-6), vascular endothelial growth factor (PI-VEGF), plasminogen activator inhibitor-1 (PI-PAI-1), transforming growth factor-β (PI-TGF-β), and cancer antigen-125 (PI-CA-125) as known markers of peritoneal fibrosis. The single nucleotide polymorphism rs5186 (A1166C) in AGT R1 gene is located in 3' untranslated region (UTR) of the gene, while polymorphism rs1799998 (T -344 C) in CYP11B2 gene is located in the promoter region of the gene. We compared marker concentrations in patients with genotype DD vs. Dd and dd for AGT R1 and patients with genotype HH vs. Hh and hh for CYP11B2. The results show that polymorphism of CYP11B2 gene is associated with serum concentration of aldosterone. Patients with genotype HH had statistically significantly lower serum concentration of aldosterone (p=0.04). These patients also showed a trend to a lower rate of production of I-IL-6 (p=0.07), which correlated with lower concentrations of PAI-1 (p=0.002) and VEGF (p=0.005). AGT R1 gene polymorphism did not show any association with studied variables. Our findings suggest the possibility of genetic predisposition for development of peritoneal fibrosis that could be important for identification of patients with an "unfavorable" genotype, which could lead to customized prescription of appropriate therapy and personalized patient management. .

Haplotype association and synergistic effect of human aldosterone synthase (CYP11B2) gene polymorphisms causing susceptibility to essential hypertension in Indian patients

ABSTRACTBackground: Aldosterone synthase (CYP11B2) is a key enzyme involved in the terminal steps of aldosterone biosynthesis. Genetic variability in CYP11B2 gene has been associated with heterogeneous aldosterone production, which can affect sodium homeostasis and thereby regulation of blood pressure. Hence, the present study was aimed to explore the single-locus variations, haplotype and epistasis patterns of CYP11B2 (C-344T, intron-2 gene conversion and Lys173Arg) gene polymorphisms, and the risk contributed by them to the development of essential hypertension (EHT). Methods: A total of 279 hypertensive patients and 200 normotensive controls were enrolled in this study. C-344T and Lys173Arg polymorphisms of CYP11B2 gene were genotyped by PCR-RFLP method and intron-2 gene conversion (IC) polymorphism by allele-specific PCR analysis. Results: Single-locus analysis revealed significant association of CYP11B2 C-344T and Lys173Arg polymorphisms with EHT (p < 0.05). Considering the sexes, Lys173 allele was found to be at risk for hypertension in males (OR 1.40; 95% CI = 1.01–1.96). Unphased haplotype analysis revealed H1 (T-Conv-Lys; p = 0.0017) to have significant risk for EHT, while haplotype H4 (T-Wt-Arg) had a significant protective effect. Multifactor dimensionality reduction (MDR) interaction analysis found the overall best model with C-344T and IC polymorphisms exhibiting strong synergistic effect. Conclusion: The present study revealed a strong synergistic effect of CYP11B2 C-344T and IC polymorphisms causing susceptibility to EHT and haplotype H1 (-344T-Conv-Lys173) as the risk-conferring factor for hypertension predisposition.