Dataset Information

Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension--a meta-regression analysis of 98 observational studies.

ABSTRACT:

Background

Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial.

Objectives

This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk.

Data sources

PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013.

Study eligibility criteria participants and interventions

Cross-sectional surveys and case-control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity.

Study appraisal and synthesis methods

The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models.

Results

ETHNICITY [ODDS RATIO (OR): 1.24; 95% confidence interval (CI): 1.08-1.42] and hypertension (OR: 1.55; 95% CI: 1.04-2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p<0.05). In subgroup analyses, this result was significant in the nondiabetic nephropathy group. Compared with the I allele, the D allele had the highest risk (OR: 3.75; 95% CI: 1.84-7.65) for CKD in hypertensive Asian males.

Conclusions and implications of key findings

The ACE I/D polymorphisms may incur the highest risk for increasing CKD in hypertensive Asian males.

SUBMITTER: Lin C

PROVIDER: S-EPMC3909221 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension--a meta-regression analysis of 98 observational studies.

Lin Chin C Yang Hsin-Yi HY Wu Chia-Chao CC Lee Herng-Sheng HS Lin Yuh-Feng YF Lu Kuo-Cheng KC Chu Chi-Ming CM Lin Fu-Huang FH Kao Sen-Yeong SY Su Sui-Lung SL

PloS one 20140131 1

<h4>Background</h4>Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial.<h4>Objectives</h4>This study investigated the gender-de ...[more]

PMID: 24498151

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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.

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:BackgroundAntihypertensive drug therapies have been reported to be associated with new onset of type 2 diabetes mellitus in some hypertensive patients after prolonged use. Angiotensin converting enzyme (ACE) gene has been found to affect essential hypertension, response of antihypertensive therapies, and glycemic disturbances. Therefore, ACE gene I/D polymorphism may be associated with risk of new onset of type 2 diabetes via metabolic disturbances, glycemic dysregulation, and insulin resistance.AimTo assess the correlation between ACE gene I/D polymorphism and glycemic disturbance under influence of diuretic and other antihypertensive drug therapies.Materials and methodsWe recruited 270 normotensive patients as control (150 men and 120 women), 270 hypertensive patients (95 men and 175 women), and 240 hypertensive with new onset of diabetes patients (80 men and 160 women). All samples were genotyped for ACE gene polymorphic alleles and relationship between different genotypes and anthropometric and clinical parameters along with drug therapies was established and analyzed.ResultsBaseline clinical (systolic blood pressure, diastolic blood pressure, and fasting blood glucose level) and anthropometric parameters (height, weight, waist circumference, hip circumference, waist-hip ratio, and body mass index) of study populations were found highly statistically significant (P < .05) when compared among study groups. Furthermore, genotype wise comparison of all these parameters in essential hypertensive (EH) and essential hypertensive with onset of diabetes (EHNOD) patients found most of them nonsignificant and no variation was found with respect to different genotypes of ACE gene. The genotype wise comparison of clinical parameters among different antihypertensive drug therapy was found statistically nonsignificant in both EH and EHNOD patients.DiscussionAnthropometric parameters can be taken as the risk indicator factors for hypertension and diabetes. However, ACE gene polymorphism may not be a risk factor for development of diabetes in hypertensive patients.ConclusionThe present study suggested that ACE gene polymorphism did not show any significant association with the risk of new onset of diabetes in EH patients and more detailed studies with large population size are needed.

Dataset Information

Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension--a meta-regression analysis of 98 observational studies.

Background

Objectives

Data sources

Study eligibility criteria participants and interventions

Study appraisal and synthesis methods

Results

Conclusions and implications of key findings

Publications

Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension--a meta-regression analysis of 98 observational studies.

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