Dataset Information

Ethnic differences in the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and peripheral vascular disease: A meta-analysis.

ABSTRACT:

Background

Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain controversial. Therefore, we conducted the current meta-analysis to evaluate this relationship in the general population of different ethnicities.

Methods

We searched PubMed, Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies. Random-effect models were applied to estimate the pooled odds ratio (OR) with a 95% confidence interval (CI), regardless of between-study heterogeneity.

Results

A total of 13 studies with 1966 cases and 6129 controls were included in this meta-analysis. The pooled ORs for the association between ACE I/D polymorphism and PVD risk were not statistically significant in the overall population under all genetic models. In further ethnicity-stratified analyses, we found a statistically significant association of ACE I/D polymorphism with PVD susceptibility in Asians under most models. However, the association among Caucasians did not reach statistical significance.

Conclusion

ACE I/D polymorphism might be associated with susceptibility to PVD in the Asian population, but there was no clear evidence indicating a similar significant relationship among Caucasians.

SUBMITTER: Han C

PROVIDER: S-EPMC5747497 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Publications

Ethnic differences in the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and peripheral vascular disease: A meta-analysis.

Han Chao C Han Xi-Kun XK Liu Fang-Chao FC Huang Jian-Feng JF

Chronic diseases and translational medicine 20170918 4

<h4>Background</h4>Several studies have investigated the association of angiotensin-converting enzyme (<i>ACE</i>) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain controversial. Therefore, we conducted the current meta-analysis to evaluate this relationship in the general population of different ethnicities.<h4>Methods</h4>We searched PubMed, Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies. Random-effe ...[more]

PMID: 29354806

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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.

Dataset Information

Ethnic differences in the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and peripheral vascular disease: A meta-analysis.

Background

Methods

Results

Conclusion

Publications

Ethnic differences in the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and peripheral vascular disease: A meta-analysis.

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