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Association between aldehyde dehydrogenase 2 genetic polymorphism and serum lipids or lipoproteins: A meta-analysis of seven East Asian populations

  • Author Footnotes
    1 These authors contributed equally.
    Pan-Pan Hao
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, China
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  • Author Footnotes
    1 These authors contributed equally.
    Li Xue
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, China
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  • Xing-Li Wang
    Affiliations
    Division of Cardiothoracic Surgery, The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
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  • Yu-Guo Chen
    Correspondence
    Corresponding author. Tel.: +86 531 82169307; fax: +86 531 82169524.
    Affiliations
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, China
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  • Jia-Li Wang
    Affiliations
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, China
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  • Wen-Qing Ji
    Affiliations
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, China
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  • Feng Xu
    Affiliations
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, China
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  • Shu-Jian Wei
    Affiliations
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, China
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  • Yun Zhang
    Correspondence
    Corresponding author. Tel.: +86 531 82169304; fax: +86 531 82169304.
    Affiliations
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, China
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  • Author Footnotes
    1 These authors contributed equally.
      Moderate alcohol consumption appears to confer some protection against coronary heart disease, which is related to changes in serum levels of lipoproteins, especially high-density lipoprotein cholesterol (HDL-C) [
      • Stampfer M.J.
      • Colditz G.A.
      • Willett W.C.
      • et al.
      A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women.
      ,
      • Rimm E.B.
      • Giovannucci E.L.
      • Willett W.C.
      • et al.
      Prospective study of alcohol consumption and risk of coronary disease in men.
      ]. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde produced from ethanol into acetate and plays a crucial role in the oxidation of acetaldehyde in vivo [
      • Bosron W.F.
      • Li T.K.
      Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism.
      ]. A sequence variant (rs671) on chromosome 12q24.2 was found associated with inactive ALDH2. A mutant allele, ALDH2*2, has a single point mutation (G to A transition in exon 12) at position 1510 of the active ALDH2*1 gene, which results in a substitution of glutamic acid 504 to lysine and produces inactive ALDH2 [
      • Crabb D.W.
      • Edenberg H.J.
      • Bosron W.F.
      • et al.
      Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant.
      ,
      • Singh S.
      • Fritze G.
      • Fang B.L.
      • et al.
      Inheritance of mitochondrial aldehyde dehydrogenase: genotyping in Chinese, Japanese and South Korean families reveals dominance of the mutant allele.
      ,
      • Xiao Q.
      • Weiner H.
      • Crabb D.W.
      The mutation in the mitochondrial aldehyde dehydrogenase (ALDH2) gene responsible for alcohol-induced flushing increases turnover of the enzyme tetramers in a dominant fashion.
      ]. The Glu504Lys variant is almost exclusively present in East Asians, and Wada et al. [
      • Wada M.
      • Daimon M.
      • Emi M.
      • et al.
      Genetic association between aldehyde dehydrogenase 2 (ALDH2) variation and high-density lipoprotein cholesterol (HDL-C) among non-drinkers in two large population samples in Japan.
      ] found no variants of rs671 in a Caucasian population. The ALDH2 genotypes are closely related to alcohol metabolism [
      • Bosron W.F.
      • Li T.K.
      Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism.
      ] and were recently found to be associated with atherosclerosis [
      • Narita M.
      • Kitagawa K.
      • Nagai Y.
      • et al.
      Effects of aldehyde dehydrogenase genotypes on carotid atherosclerosis.
      ], hypertension [
      • Takagi S.
      • Baba S.
      • Iwai N.
      • et al.
      The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese but does not alter the sensitivity to pressor effects of alcohol: the Suita study.
      ,
      • Amamoto K.
      • Okamura T.
      • Tamaki S.
      • et al.
      Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population.
      ,
      • Chen L.
      • Davey Smith G.
      • Harbord R.M.
      • et al.
      Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach.
      ], and myocardial infarction [
      • Takagi S.
      • Iwai N.
      • Yamauchi R.
      • et al.
      Aldehyde dehydrogenase 2 gene is a risk factor for myocardial infarction in Japanese men.
      ,
      • Jo S.A.
      • Kim E.K.
      • Park M.H.
      • et al.
      A Glu487Lys polymorphism in the gene for mitochondrial aldehyde dehydrogenase 2 is associated with myocardial infarction in elderly Korean men.
      ] in Asians. The risks have been attributed primarily to an increase in serum HDL-C level. Recently, we reported an association of ALDH2 deficiency and increased risk of type II diabetes mellitus in female patients with coronary artery disease but not levels of serum lipids and/or lipoproteins or coronary atherosclerosis severity [
      • Xu F.
      • Chen Y.G.
      • Geng Y.J.
      • et al.
      The polymorphism in acetaldehyde dehydrogenase 2 gene, causing a substitution of Glu > Lys(504), is not associated with coronary atherosclerosis severity in Han Chinese.
      ,
      • Xu F.
      • Chen Y.
      • Lv R.
      • et al.
      ALDH2 genetic polymorphism and the risk of type II diabetes mellitus in CAD patients.
      ]. The reason for the discrepancy is unclear but may be related to low statistical power or to differences among the ethnic groups studied.

      Keywords

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