Association between ALDH2 Gene Polymorphism and Late-onset Alzheimer Disease: An Up-to-date Meta-analysis

Author(s): Haitao Liu, Wei Ge*, Wei Chen, Xue Kong, Weiming Jian, Anhui Wang.

Journal Name: Current Alzheimer Research

Volume 17 , Issue 2 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Objectives: Previous case-control studies have focused on the relationship between ALDH2 gene polymorphism and late-onset Alzheimer's Disease (LOAD), but no definite unified conclusion has been reached. Therefore, the correlation between ALDH2 Glu504Lys polymorphism and LOAD remains controversial. To analyze the correlation between ALDH2 polymorphism and the risk of LOAD, we implemented this up-to-date meta-analysis to assess the probable association.

Methods: Studies were searched through China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, China Biology Medicine, PubMed, Cochrane Library, Clinical- Trials.gov, Embase, and MEDLINE from January 1, 1994 to December 31, 2018, without any restrictions on language and ethnicity.

Results: Five studies of 1057 LOAD patients and 1136 healthy controls met our criteria for the analysis. Statistically, the ALDH2 GA/AA genotype was not linked with raising LOAD risk (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 0.96-2.28, p = 0.07). In subgroup analysis, the phenomenon that men with ALDH2*2 had higher risk for LOAD (OR = 1.72, 95%CI = 1.10-2.67, p = 0.02) was observed.

Conclusion: This study comprehends only five existing case-control studies and the result is negative. The positive trend might appear when the sample size is enlarged. In the future, more large-scale casecontrol or cohort studies should be done to enhance the association between ALDH2 polymorphism and AD or other neurodegenerative diseases.

Keywords: Alzheimer disease, ALDH2, gene polymorphism, case-control study, up-to-date, meta-analysis.

[1]
Chiba-Falek O, Lutz MW. Towards precision medicine in Alzheimer’s disease: deciphering genetic data to establish informative biomarkers. Expert Rev Precis Med Drug Dev 2(1): 47-55. (2017).
[http://dx.doi.org/10.1080/23808993.2017.1286227] [PMID: 28944295]
[2]
Zusso M, Barbierato M, Facci L, Skaper SD, Giusti P. Neuroepigenetics and Alzheimer’s disease: an update. J Alzheimers Dis 64(3): 671-88. (2018).
[http://dx.doi.org/10.3233/JAD-180259] [PMID: 29991138]
[3]
Wang S, Ge W, Harns C, Meng X, Zhang Y, Ren J. Ablation of toll-like receptor 4 attenuates aging-induced myocardial remodeling and contractile dysfunction through NCoRI-HDAC1-mediated regulation of autophagy. J Mol Cell Cardiol 119: 40-50. (2018).
[http://dx.doi.org/10.1016/j.yjmcc.2018.04.009] [PMID: 29660306]
[4]
Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev 94(1): 1-34. (2014).
[http://dx.doi.org/10.1152/physrev.00017.2013] [PMID: 24382882]
[5]
Deza-Ponzio R, Herrera ML, Bellini MJ, Virgolini MB, Hereñú CB. Aldehyde dehydrogenase 2 in the spotlight: The link between mitochondria and neurodegeneration. Neurotoxicology 68: 19-24. (2018).
[http://dx.doi.org/10.1016/j.neuro.2018.06.005] [PMID: 29936317]
[6]
D’Souza Y, Elharram A, Soon-Shiong R, Andrew RD, Bennett BM. Characterization of Aldh2 (-/-) mice as an age-related model of cognitive impairment and Alzheimer’s disease. Mol Brain 8: 27-42. (2015).
[http://dx.doi.org/10.1186/s13041-015-0117-y] [PMID: 25910195]
[7]
Wang J, Du H, Jiang L, et al. Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure. Proc Natl Acad Sci USA 110(35): 14444-9. (2013).
[http://dx.doi.org/10.1073/pnas.1306011110] [PMID: 23940368]
[8]
Zhao Y, Wang C. Glu504Lys single nucleotide polymorphism of aldehyde dehydrogenase 2 gene and the risk of human diseases. BioMed Res Int 2015174050 (2015).
[http://dx.doi.org/10.1155/2015/174050] [PMID: 26491656]
[9]
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 273(1): 192-6. (2000).
[http://dx.doi.org/10.1006/bbrc.2000.2923] [PMID: 10873585]
[10]
Ma L, Lu ZN. Role of ADH1B rs1229984 and ALDH2 rs671 gene polymorphisms in the development of Alzheimer's disease. Genet Mol Res 15(4): 05-12. (2016).
[11]
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 268(1-2): 172-5. (2008).
[http://dx.doi.org/10.1016/j.jns.2007.12.006] [PMID: 18201725]
[12]
Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods 11(2): 193-206. (2006).
[http://dx.doi.org/10.1037/1082-989X.11.2.193] [PMID: 16784338]
[13]
Zhou S, Huriletemuer , Wang J, et al. Absence of association on aldehyde dehydrogenase 2 (ALDH2) polymorphism with Mongolian Alzheimer patients. Neurosci Lett 468(3): 312-5. (2010).
[http://dx.doi.org/10.1016/j.neulet.2009.11.022] [PMID: 19914339]
[14]
Komatsu M, Shibata N, Ohnuma T, et al. Polymorphisms in the aldehyde dehydrogenase 2 and dopamine β hydroxylase genes are not associated with Alzheimer’s disease. J Neural Transm 121(4): 427-32. (2014).
[15]
Hao PP, Chen YG, Wang JL, Wang XL, Zhang Y. Meta-analysis of aldehyde dehydrogenase 2 gene polymorphism and Alzheimer’s disease in East Asians. Can J Neurol Sci 38(3): 500-6. (2011).
[http://dx.doi.org/10.1017/S0317167100011938]
[16]
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 25(3): 295-301. (2004).
[http://dx.doi.org/10.1016/S0197-4580(03)00114-3] [PMID: 15123334]
[17]
Kamino K, Tanaka T, Kida T, et al. [The role of lipid metabolism in Alzheimer’s disease]. Nihon Shinkei Seishin Yakurigaku Zasshi 22(4): 103-10. (2002).
[PMID: 12373863]
[18]
Kanamaru T, Kamimura N, Yokota T, et al. Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer’s disease. Neurosci Lett 587: 126-31. (2015).
[http://dx.doi.org/10.1016/j.neulet.2014.12.033] [PMID: 25529196]
[19]
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 Alzheimers Dis 9(2): 155-66. (2006).
[http://dx.doi.org/10.3233/JAD-2006-9208] [PMID: 16873963]
[20]
Nichols E, Szoeke CEI, Vollset SE, Abbasi N, Abd-Allah F, Abdela J, et al. GBD 2016 Dementia Collaborators. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 18(1): 88-106. (2019).
[http://dx.doi.org/10.1016/S1474-4422(18)30403-4] [PMID: 30497964]
[21]
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 28(24): 6239-49. (2008).
[http://dx.doi.org/10.1523/JNEUROSCI.4956-07.2008] [PMID: 18550766]
[22]
Bai J, Mei Y. Overexpression of aldehyde dehydrogenase-2 attenuates neurotoxicity induced by 4-hydroxynonenal in cultured primary hippocampal neurons. Neurotox Res 19(3): 412-22. (2011).
[http://dx.doi.org/10.1007/s12640-010-9183-1] [PMID: 20361289]
[23]
Joshi AU, Van Wassenhove LD, Logas KR, et al. Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer’s disease related pathology. Acta Neuropathol Commun 7(1): 190. (2019).
[http://dx.doi.org/10.1186/s40478-019-0839-7] [PMID: 31829281]
[24]
Chang YH, Lee SY, Wang TY, et al. Comorbid alcohol dependence disorder may be related to aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) in bipolar II disorder, but only to ALDH2 in bipolar I disorder, in Han Chinese. Bipolar Disord 17(5): 536-42. (2015).
[http://dx.doi.org/10.1111/bdi.12313] [PMID: 26033520]
[25]
Ohsawa I, Kamino K, Nagasaka K, et al. Genetic deficiency of a mitochondrial aldehyde dehydrogenase increases serum lipid peroxides in community-dwelling females. J Hum Genet 48(8): 404-9. (2003).
[http://dx.doi.org/10.1007/s10038-003-0046-y] [PMID: 12905081]
[26]
Ohta S, Ohsawa I, Kamino K, Ando F, Shimokata H. Mitochondrial ALDH2 deficiency as an oxidative stress. Ann N Y Acad Sci 1011: 36-44. (2004).
[http://dx.doi.org/10.1196/annals.1293.004] [PMID: 15126281]
[27]
Chen CH, Joshi AU, Mochly-Rosen D. The role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in neuropathology and neurodegeneration. Acta Neurol Taiwan 25(44): 111-23. (2016).
[28]
Aoki Y, Wehage SL, Talalay P. Quantification of skin erythema response to topical alcohol in alcohol-intolerant East Asians. Skin Res Technol 23(4): 593-6. (2017).
[29]
Greene CS, Penrod NM, Williams SM, Moore JH. Failure to replicate a genetic association may provide important clues about genetic architecture. PLoS One 4(6)e5639 (2009).
[http://dx.doi.org/10.1371/journal.pone.0005639] [PMID: 19503614]
[30]
Dupré N. Genetic susceptibility of Alzheimer’s disease in East Asia. Can J Neurol Sci 38(3): 394-5. (2011).
[http://dx.doi.org/10.1017/S0317167100011768]
[31]
Li D, Zhao H, Gelernter J. Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians. Hum Genet 131(5): 725-37. (2012).
[http://dx.doi.org/10.1007/s00439-011-1116-4] [PMID: 22102315]
[32]
Heymann D, Stern Y, Cosentino S, Tatarina-Nulman O, Dorrejo JN, Gu Y. The association between alcohol use and the progression of Alzheimer’s disease. Curr Alzheimer Res 13(12): 1356-62. (2016).
[http://dx.doi.org/10.2174/1567205013666160603005035] [PMID: 27628432]
[33]
Brzecka A, Leszek J, Ashraf GM, et al. Sleep disorders associated with Alzheimer’s disease: a perspective. Front Neurosci 12: 330. (2018).
[http://dx.doi.org/10.3389/fnins.2018.00330] [PMID: 29904334]
[34]
Liang X, Chen Z, Dong X, et al. Mental work demands and late-life cognitive impairment: results from the shanghai aging study. J Aging Health 31(5): 883-98. (2019).
[http://dx.doi.org/10.1177/0898264318765034] [PMID: 29661060]
[35]
Milne R, Diaz A, Badger S, Bunnik E, Fauria K, Wells K. At, with and beyond risk: expectations of living with the possibility of future dementia. Sociol Health Illn 40(6): 969-87. (2018).
[http://dx.doi.org/10.1111/1467-9566.12731] [PMID: 29659032]
[36]
Xu W, Wang H, Wan Y, et al. Alcohol consumption and dementia risk: a dose-response meta-analysis of prospective studies. Eur J Epidemiol 32(1): 31-42. (2017).
[http://dx.doi.org/10.1007/s10654-017-0225-3] [PMID: 28097521]
[37]
Namboori PK, Vineeth KV, Rohith V, et al. The ApoE gene of Alzheimer’s disease (AD). Funct Integr Genomics 11(4): 519-22. (2011).
[http://dx.doi.org/10.1007/s10142-011-0238-z] [PMID: 21769591]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 2
Year: 2020
Page: [105 - 111]
Pages: 7
DOI: 10.2174/1567205017666200317102337
Price: $65

Article Metrics

PDF: 11