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Associations of Angiotensin-Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta-Analysis.

ABSTRACT: There have been numerous studies concerning the associations of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D), angiotensin II receptor 1 (AT1R) gene A1166C, and endothelial nitric oxide synthase (eNOS) gene 4b/a polymorphisms with risk of pregnancy hypertensive disorders (PHDs). However, the results are inconsistent. A total of 83 eligible studies (10,354/18,446 cases/controls) were included in this meta-analysis. Pooled odds ratios with corresponding 95% confidence intervals were used to calculate these associations. The effects of ethnicity and types of PHDs were also considered. Results showed significant associations between the ACE gene polymorphism and PHDs in all of the populations except that in Africa. The associations also existed in AT1R, eNOS gene polymorphism and PHDs in part of the gene models in the overall population. These results indicated the ACE gene polymorphism was associated with an increased risk of PHDs, whereas the eNOS and AT1R gene polymorphism only have increased susceptibility to PHDs in part of the gene models.

SUBMITTER: Gong FF

PROVIDER: S-EPMC8031698 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Associations of Angiotensin-Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta-Analysis.

Gong Feng-Feng FF Hu Cai-Yun CY Lu Shan-Shan SS Qian Zhen-Zhong ZZ Feng Fang F Wu Yi-Le YL Yang Hui-Yun HY Sun Ye-Huan YH

Journal of clinical hypertension (Greenwich, Conn.) 20150629 12

There have been numerous studies concerning the associations of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D), angiotensin II receptor 1 (AT1R) gene A1166C, and endothelial nitric oxide synthase (eNOS) gene 4b/a polymorphisms with risk of pregnancy hypertensive disorders (PHDs). However, the results are inconsistent. A total of 83 eligible studies (10,354/18,446 cases/controls) were included in this meta-analysis. Pooled odds ratios with corresponding 95% confidence intervals ...[more]

PMID: 26119526

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Project description:ObjectiveA silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle.MethodsFifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc.ResultsCycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and -3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon.ConclusionThe observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism.

Project description:Background and purposeThe angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs.MethodsThe CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes.ResultsAmong 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02).ConclusionThe progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association.

Project description:IntroductionAlthough the pathophysiological mechanism of hypertension is not fully elucidated yet, a large number of pieces of evidence have shown that genetic alterations in the renin-angiotensin-aldosterone system play a central role. However, the association of insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene with essential hypertension is controversial yet, and there is a limited number of publications among the Ethiopian population. Therefore, this study aimed to determine the association of ACE gene I/D polymorphism with the risk of hypertension among essential hypertension patients at the University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia.Materials and methodsA case-control study was conducted from October 07, 2020, to June 02, 2021, among hypertensive patients and normotensive control groups at the University of Gondar Comprehensive Specialized Hospital. A structured questionnaire was used to collect socio-demographic data and anthropometric measurements. Five milliliters of blood were drawn from each of the randomly selected 64 hypertensive and 64 normotensive participants for molecular test analysis. Genetic polymorphism of the ACE gene was identified using polymerase chain reaction (PCR) and electrophoresis. Data analysis was done using SPSS version 25.0 software. The strength of association between the genotype and hypertension was estimated through the calculation of adjusted odds ratio and 95% confidence intervals using logistic regression. P-value < 0.05 was considered statistically significant.ResultThe distribution of DD genotypes and D allele of the ACE gene were 48.4% and 63% in essential hypertensive patients, respectively, while it were 29.7% and 42.2% in control subjects respectively. The ACE DD genotype (p-value = 0.005) and D allele (p-value = 0.001) were more frequent among hypertensive patients as compared to controls.ConclusionThe present study found that the DD genotype and D allele of the ACE gene has had a strong association with a high risk of hypertension in the study population.

Dataset Information

Associations of Angiotensin-Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta-Analysis.

Publications

Associations of Angiotensin-Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta-Analysis.

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