title: East asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: possible roles of reactive aldehydes and implications of alcohol flushing syndrome.
abstract: BACKGROUND
  Coronary spastic angina (CSA) is a common disease among East Asians, including Japanese. The prevalence of alcohol flushing syndrome associated with deficient activity of the variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is prevalent among East Asians. We examined whether CSA is associated with the ALDH2*2 genotype in Japanese.
  
  
  RESULTS
  The study subjects consisted of 202 patients in whom intracoronary injection of acetylcholine was performed by angiography on suspicion of CSA (119 men and 83 women; mean age, 66.2±11.4 years). They were divided into CSA (112 patients) and control groups (90 patients). ALDH2 genotyping was performed by the direct application of the TaqMan polymerase chain reaction system on dried whole blood. Clinical and laboratory data were examined using conventional methods. The frequencies of male sex, ALDH2*2 genotype carriers, alcohol flushing syndrome, tobacco smoking, and the plasma level of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, and P=0.007, respectively) and the plasma high-density lipoprotein cholesterol levels were lower (P<0.001) in the CSA group than in the control group. The multivariable logistic regression analysis revealed that ALDH2*2 genotype and smoking were significantly associated with CSA (P<0.001 and P=0.024, respectively).
  
  
  CONCLUSIONS
  East Asian variant ALDH2*2 genotypes and, hence, deficient ALDH2 activity were associated with CSA in Japanese. These data support further investigation of treatment targeting aldehydes for CSA.
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Eisaku
authors.initials: E
authors.lastname: Harada
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Sumio
authors.initials: S
authors.lastname: Morita
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Kenji
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Mariko
authors.initials: M
authors.lastname: Hayashida
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Makoto
authors.initials: M
authors.lastname: Shono
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Morikawa
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.).
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: From Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan (Y.M., E.H., S.M., M.S., H.Y.); Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan (S.M., T.M.); School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Japan (K.K., M.H.); Division of Cardiovascular Medicine, Nara City Hospital, Nara, Japan (Y.M.); Nakayama Cardiovascular Clinic, Amakusa, Japan (M.N.); and Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan (M.Y.). yasue@juryo.or.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasue
mesh_terms: D000109:Acetylcholine; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000000981:diagnostic imaging / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D003331:Coronary Vessels; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005483:Flushing / Q000139:chemically induced*; D005838:Genotype; D006801:Humans; D007269:Injections, Intra-Arterial; D007564:Japan; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D014527:Uric Acid / Q000097:blood
chemical_list: D000447:Aldehydes; D008076:Cholesterol, HDL; D014527:Uric Acid; D000431:Ethanol; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000109:Acetylcholine
keywords: alcohol; aldehyde dehydrogenase; coronary spasm; coronary spastic angina