Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: A meta-analysis
ABSTRACT Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for alcohol metabolism in humans. Emerging evidences have shown that functional polymorphisms in ADH and ALDH genes might play a critical role in increasing coronary artery disease (CAD) and myocardial infarction (MI) risks; however, individually published studies showed inconclusive results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of ADH and ALDH genes with susceptibility to CAD and MI. A literature search was conducted on PubMed, Embase, Web of Science and Chinese BioMedical databases from inception through December 1st, 2012. Crude relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Twelve case-control studies were included with a total of 9,616 subjects, including 2,053 CAD patients, 1,436 MI patients, and 6,127 healthy controls. Meta-analysis showed that mutant genotypes (GA+AA) of the rs671 polymorphism in the ALDH2 gene were associated with increased risk of both CAD and MI (CAD: RR=1.20, 95%CI: 1.03-1.40, P=0.021; MI: RR=1.32, 95%CI: 1.11-1.57, P=0.002). However, there were no significant associations of ADH genetic polymorphisms to CAD and MI risks (CAD: RR=0.92, 95%CI: 0.73-1.15, P=0.445; MI: RR=0.93, 95%CI: 0.84-1.03, P=0.148). In conclusion, this meta-analysis provides strong evidence that ALDH2 rs671 polymorphism may be associated with increased risks of CAD and MI. However, further studies are still needed to accurately determine whether ADH genetic polymorphisms are associated with susceptibility to CAD and MI.
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ABSTRACT: This study aimed to compare the accuracy and performance of four genotyping methods for detecting single nucleotide polymorphisms (SNPs) in aldehyde dehydrogenase-2 (ALDH2), which is the principal enzyme involved in alcohol metabolism. We genotyped rs671 of ALDH2 in 96 coronary heart disease (CHD) patients with four methods including high resolution melting analysis (HRM), TaqMan allelic discrimination assay (TaqMan), allele-specific PCR (AS-PCR) and pyrosequencing. Meanwhile, we compared the accuracy and performance of these methods. All selected patients were successfully genotyped with referred methods. The results of these four assays showed 100% concordant results and had 100% accuracy as verified by Sanger sequencing. All of the referred methods can be used for genotyping ALDH2 rs671 with the same accuracy compared to Sanger sequencing. In small size of clinical samples, HRM and AS-PCR outperform over others due to their lower cost and less hands-on operation, which are suitable for clinical application.PLoS ONE 03/2015; 10(3):e0122745. DOI:10.1371/journal.pone.0122745 · 3.53 Impact Factor
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ABSTRACT: Objective Coronary artery disease (CAD) is a multifactorial and polygenic disease. The aim of this study was to examine the association between six polymorphisms of four alcohol metabolism relevant genes (ADH1B, ADH1C, ALDH1b1, ALDH2) and the risk of CAD in Han Chinese. Methods and Results This was a hospital-based case-control study involving 1365 hypertensive patients. All study subjects were angiographically confirmed. Genotypes were determined with ligase detection reaction method. There was no observable deviation from the Hardy-Weinberg equilibrium for six examined polymorphisms in controls. The genotype and allele distributions of ALDH1b1 rs2073478 and ALDH2 rs671 polymorphisms differed significantly between the two groups (P≤0.005), even after the Bonferroni correction. The most common allele combination was A-C-C-G-C-G (alleles in order of rs1229984, rs1693482, rs2228093, rs2073478, rs886205, rs671) and its frequency was slightly higher in controls than in CAD patients (P = 0.067). After assigning the most common allele combination as a reference, allele combination A-C-C-T-C-A, which simultaneously possessed the risk alleles of rs2073478 and rs671 polymorphisms, was associated with a 1.80-fold greater risk of CAD. Further, a two-locus model including rs2073478 and rs671 that had a maximal testing accuracy of 0.598 and a cross-validation consistency of 10 (P = 0.008) was deemed as the overall best MDR model, which was further validated by classical Logistic regression model. Conclusion Our findings provide clear evidence for both individual and interactive associations of ALDH1b1 and ALDH2 genes with the development of CAD in Han Chinese.PLoS ONE 07/2014; 9(7):e103161. DOI:10.1371/journal.pone.0103161 · 3.53 Impact Factor
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ABSTRACT: BACKGROUND: -While moderate alcohol use is associated with protection against myocardial infarction (MI), it is not known whether this effect is generalizable to populations worldwide. It is also uncertain whether differences in the pattern of alcohol use (and in particular heavy episodic consumption) between different regions negates any beneficial effect. METHODS AND RESULTS: -We included 12,195 cases of first MI and 15,583 age- and sex-matched controls from 52 countries. Current alcohol use was associated with a reduced risk of MI (compared to non-users, adjusted odds ratio 0.87; 95% CI 0.80-0.94, p=0.001), however the strength of this assocation was not uniform across different regions (region-alcohol interaction p<0.001). Heavy episodic drinking (>/=6 drinks) within the preceding 24 hours was associated with an increased risk of MI (odds ratio 1.4; 95% CI 1.1-1.9, p=0.01). This risk was particularly elevated in older individuals (for age >65 years, odds ratio 5.3; 95% CI 1.6-18, p=0.008). CONCLUSIONS: -In most participants, low levels of alcohol use are associated with a moderate reduction in the risk of MI, however the strength of this association may not be uniform across different countries. An episode of heavy drinking is associated with an increased risk of acute MI in the subsequent 24 hours, particularly in older individuals.Circulation 07/2014; 130(5). DOI:10.1161/CIRCULATIONAHA.113.007627 · 14.95 Impact Factor