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Meta-Analysis of Aldehyde Dehydrogenase 2 Gene Polymorphism and Alzheimer's Disease in East Asians

  • Pan-Pan Hao (a1), Yu-Guo Chen (a1), Jia-Li Wang (a1), Xing Li Wang (a2) and Yun Zhang (a1)...



The association of genetic polymorphism of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and Alzheimer's disease (AD) has been controversial and has been investigated only in several small-sample studies. In the present study, we performed a meta-analysis to evaluate the cross-sectional association of ALDH2 variants and AD risk in East Asian populations.


Trials were retrieved through MEDLINE, EMBASE, J-STAGE and the China National Knowledge Internet databases (from January 1, 1994 to November 1, 2010) without any restriction on language. Data were abstracted by a standardized protocol.


We found four studies of 821AD patients and 1380 healthy controls that qualified for the analysis. The variant ALDH2 genotype GA/AA was not associated with increased AD risk (odds ratio (OR) = 1.35; 95% confidence interval (CI) = 0.75-2.42; p = 0.32), even after stratification for the status of apolipoprotein E epsilon 4 allele. However, in the subgroup analyses, the association was significant for men (OR = 1.72; 95% CI = 1.10-2.67; p = 0.02).


This study adds to the evidence that ALDH2 GA/AA genotype increases the risk of AD among East Asian men, although the effect size is moderate.

Résumé: Contexte:

L’association entre le polymorphisme du gene de l’aldehyde deshydrogenase 2 (ALDH2) et la maladie d’Alzheimer (MA) est controversee et elle a ete examinee seulement au cours d’etudes faites chez un petit nombre de sujets. Nous avons effectue une meta-analyse pour evaluer l’association transversale de variations dans le gene de l’ALDH2 et le risque de MA dans des populations de l’Asie de l‘Est.


Nous avons identifie les etudes dans MEDLINE, EMBASE, J-STAGE et dans les bases de donnees de China National Knowledge Internet, du 1er janvier 1994 au 1er novembre 2010, sans restriction quant a la langue de publication. Les donnees ont ete recueillies selon un protocole standardise.


Nous avons identifie 4 etudes portant sur un total de 821 patients atteints de MA et 1380 temoins en bonne sante, qui rencontraient les criteres etablis pour l’analyse. La variante genotypique GA/AA du gene de l’ALDH2 n’etait pas associee a un risque accru de MA(RC = 1,35; IC a 95% : 0,75 a 2,42; p = 0,32), meme apres ajustement pour la presence de l’allele epsilon 4 du gene de l’apolipoproteine E. Cependant, dans les analyses de sous-groupes, l’association etait significative chez les hommes (RC = 1,72 ; IC a 95% : 1,10 a 2,67; p = 0,02).


Cette etude appuie la notion que le genotype GA/AA du gene de l’ALDH2 augmente le risque de MA chez les hommes de l’Asie de l‘Est, mais que cet effet est modere.

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Corresponding author

Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, No. 107, Wen Hua Xi Road, Jinan 250012, China. Pan-Pan Hao and Jia-Li contributed to this work equally.


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1 Blacker, D, Haines, JL, Rodes, L, et al. ApoE-4 and age at onset of Alzheimer’s disease: the NIMH genetics initiative. Neurology. 1997;48(1):139–47.
2 Hosoda, A, Inoue, T, Mao, CC, et al. Polymorphisms in the human apolipoprotein E receptor 2 gene in Japanese sporadic Alzheimer’s disease patients. Biosci Biotechnol Biochem. 2010: 74(3):677–9.
3 Ohta, S, Ohsawa, I. Dysfunction of mitochondria and oxidative stress in the pathogenesis of Alzheimer’s disease: on defects in the cytochrome c oxidase complex and aldehyde detoxification. J Alzheimer’s Dis. 2006;9(2):155–66.
4 Tanzi, RE, Bertram, L. New frontiers in Alzheimer’s disease genetics. Neuron. 2001;32(2):181–4.
5 Picklo, MJ, Olson, SJ, Markesbery, WR, Montine, TJ. Expression and activities of aldo-keto oxidoreductases in Alzheimer disease. J Neuropathol Exp Neurol. 2001;60(7):686–95.
6 Chen, CH, Budas, GR, Churchill, EN, Disatnik, MH, Hurley, TD, Mochly-Rosen, D. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science. 2008;321(5895): 1493–5.
7 Li, Y, Zhang, D, Jin, W, et al. Mitochondrial aldehyde dehydrogenase- 2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin. J Clin Invest. 2006;116(2):506–11.
8 Michel, TM, Gsell, W, Kasbauer, L, et al. Increased activity of mitochondrial aldehyde dehydrogenase (ALDH) in the putamen of individuals with Alzheimer’s disease: a human postmortem study. J Alzheimers Dis. 2010;19(4):1295–301.
9 Wang, B, Wang, J, Zhou, S, et al. The association of mitochondrial aldehyde dehydrogenase gene (ALDH2) polymorphism with susceptibility to late-onset Alzheimer’s disease in Chinese. J Neurol Sci. 2008;268(1-2):172–5.
10 Kamino, K, Nagasaka, K, Imagawa, M, et al. Deficiency in mitochondrial aldehyde dehydrogenase increases the risk for late-onset Alzheimer’s disease in the Japanese population. Biochem Biophys Res Commun. 2000;273(1):192–6.
11 Kim, JM, Stewart, R, Shin, IS, Jung, JS, Yoon, JS. Assessment of association between mitochondrial aldehyde dehydrogenase polymorphism and Alzheimer’s disease in an older Korean population. Neurobiol Aging. 2004;25(3):295301.
12 Shin, IS, Stewart, R, Kim, JM, et al. Mitochondrial aldehyde dehydrogenase polymorphism is not associated with incidence of Alzheimer’s disease. Int J Geriatr Psychiatry. 2005;20(11): 1075–80.
13 Zhou, S, Huriletemuer, , Wang, J, et al. Absence of association on aldehyde dehydrogenase 2 (ALDH2) polymorphism with Mongolian Alzheimer patients. Neurosci Lett. 2010;468(3): 312–15.
14 Higgins, JP, Thompson, SG, Deeks, JJ, Altman, DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.
15 Cohn, LD, Becker, BJ. How meta-analysis increases statistical power. Psychol Methods. 2003;8(3):243–53.
16 Butterworth, RF. Pathophysiology of alcoholic brain damage: synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease. Metab Brain Dis. 1995;10(1):18.
17 Freund, G, Ballinger, WE Jr. Alzheimer’s disease and alcoholism: possible interactions. Alcohol. 1992;9(3):233–40.
18 Mann, K, Widmann, U. The neurobiology of alcoholism. Neuropathology and CT/NMR findings. Fortschr Neurol Psychiatr. 1995;63(6):238–47.
19 Goedde, HW, Agarwal, DP, Harada, S, et al. Population genetic studies on aldehyde dehydrogenase isozyme deficiency and alcohol sensitivity. Am J Hum Genet. 1983;35(4):769–72.
20 Stewart, MJ, Malek, K, Crabb, DW. Distribution of messenger RNAs for aldehyde dehydrogenase 1, aldehyde dehydrogenase 2, and aldehyde dehydrogenase 5 in human tissues. J Investig Med. 1996;44(2):42–6.
21 Tan, EC, Lim, L, Leong, JY, et al. Alcohol and aldehyde dehydrogenase polymorphisms in Chinese and Indian populations. Subst Use Misuse. 2010;45(1-2):114.
22 Butterfield, DA, Bader Lange, ML, Sultana, R. Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer’s disease. Biochim Biophys Acta. 2010;1801(8):924–9.
23 Ohsawa, I, Nishimaki, K, Murakami, Y, Suzuki, Y, Ishikawa, M, Ohta, S. Age-dependent neurodegeneration accompanying memory loss in transgenic mice defective in mitochondrial aldehyde dehydrogenase 2 activity. J Neurosci. 2008;28(24):6239–49.
24 Bai, J, Mei, Y. Overexpression of aldehyde dehydrogenase-2 attenuates neurotoxicity induced by 4-hydroxynonenal in cultured primary hippocampal neurons. 2010 Apr 2. [Epub ahead of print].
25 Olafsdottir, H, Raitasalo, K, Greenfield, TK, Allamani, A. Concern about family members’ drinking and cultural consistency: a Multi-Country GENACIS Study. Contemp Drug Probl. 2009;36 (1):1.
26 Perera, B, Fonseka, P, Ekanayake, R, Lelwala, E. Smoking in adults in Sri Lanka: prevalence and attitudes. Asia Pac J Public Health. 2005;17(1):40–5.
27 Tyas, SL, Koval, JJ, Pederson, LL. Does an interaction between smoking and drinking influence the risk of Alzheimer’s disease? Results from three Canadian data sets. Stat Med. 2000;19(11-12):1685–96.
28 Greene, CS, Penrod, NM, Williams, SM, Moore, JH. Failure to replicate a genetic association may provide important clues about genetic architecture. PLoS One. 2009;4(6):e5639.
29 Chen, JH, Lin, KP, Chen, YC. Risk factors for dementia. J Formos Med Assoc. 2009;108(10):754–64.
30 Stern, Y, Gurland, B, Tatemichi, TK, Tang, MX, Wilder, D, Mayeux, R. Influence of education and occupation on the incidence of Alzheimer’s disease. JAMA. 1994;271(13):1004–10.
31 Wen, J, Ren, Y, Wang, L, et al. The reporting quality of meta-analyses improves: a random sampling study. J Clin Epidemiol. 2008;61 (8):770–5.


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