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The ALDH2*2 mutations are found in approximately 45% of East Asians, with 40% being heterozygous (HE) <jats:italic>ALDH2*1\/*2<\/jats:italic> and 5% homozygous (HO) <jats:italic>ALDH2*2\/*2<\/jats:italic>. Studies have shown that HO mice lack cardioprotective effects induced by moderate alcohol consumption. However, the impact of moderate alcohol consumption on cardiac function in HE mice is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, HO, HE, and wild\u2010type (WT) mice were subjected to a 6\u2010week moderate alcohol drinking protocol, following which myocardial tissue and cardiomyocytes of the mice were extracted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that moderate alcohol exposure did not increase mortality, myocardial fibrosis, apoptosis, or inflammation in HE mice, which differs from the effects observed in HO mice. After exposure to the 6\u2010week alcohol drinking protocol, there was impaired cardiac function, cardiomyocyte contractility, and intracellular Ca<jats:sup>2+<\/jats:sup> homeostasis and mitochondrial function in both HE and HO mice as compared to WT mice. Moreover, these animals showed overt oxidative stress production and increased levels of the activated forms of calmodulin\u2010dependent protein kinase II (CaMKII) and ryanodine receptor type 2 (RYR2) phosphorylation protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We found that moderate alcohol exposure impaired cardiac function in HE mice, possibly by increasing reactive oxygen species (ROS)\/CaMKII\/RYR2\u2010mediated Ca<jats:sup>2+<\/jats:sup> handling abnormalities. Hence, we advocate that people with <jats:italic>ALDH2<\/jats:italic>*1\/*2 genotypes rigorously avoid alcohol consumption to prevent potential cardiovascular harm induced by moderate alcohol consumption.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14811","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T05:45:09Z","timestamp":1647927909000},"page":"707-723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact and potential mechanism of effects of chronic moderate alcohol consumption on cardiac function in aldehyde dehydrogenase 2 gene heterozygous mice"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-6810","authenticated-orcid":false,"given":"Qinfeng","family":"Hu","sequence":"first","affiliation":[{"name":"Institutes of Biomedical Sciences Fudan University  Shanghai 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