Abstract
Vascular dementia is the second common cause of dementia, only second to Alzheimer’s disease in later life. The Apolipoprotein E (ApoE) gene polymorphism as a risk factor in vascular dementia has been suggested, but direct evidence from genetic association studies remains inconclusive even in Chinese population. Therefore, we performed this meta-analysis in order to evaluate the relationship between ApoE gene polymorphism and susceptibility to vascular dementia in Chinese population by pooling data from all relevant case–control studies published domestically and abroad from January 1990 to May 2011. 18 case–control studies were selected. Meta-analysis results showed that the pooled OR value of vascular dementia subjects in Chinese population with ε4 allele carriers was 2.07 [95% CI (1.69, 2.53)], and the pooled OR value of vascular dementia subjects with E4/E4 genotype was 3.34 [95% CI (1.89, 5.88)]. These results suggest that ApoE polymorphism is significantly associated with susceptibility to vascular dementia in Chinese population. The subject with at least one ε4 allele or E4/E4 genotype has higher risk suffering from vascular dementia than others.
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Baum L, Lam LC, Kwok T, Lee J, Chiu HF, Mok VC, Wong A, Chen X, Cheung WS, Pang CP, Ma SL, Tang NL, Wong KS, Ng HK (2006) Apolipoprotein E epsilon4 allele is associated with vascular dementia. Dement Geriatr Cogn Disord 22(4):301–305
Chuang YF, Hayden KM, Norton MC, Tschanz J, Breitner JC, Welsh-Bohmer KA, Zandi PP (2010) Association between APOE epsilon4 allele and vascular dementia: the Cache County study. Dement Geriatr Cogn Disord 29(3):248–253
Davidson Y, Gibbons L, Purandare N, Byrne J, Hardicre J, Wren J, Payton A, Pendleton N, Horan M, Burns A, Mann DM (2006) Apolipoprotein E epsilon4 allele frequency in vascular dementia. Dement Geriatr Cogn Disord 22(1):15–19
Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8(1):1–21
de Leeuw FE, Richard F, de Groot JC, van Duijn CM, Hofman A, van Gijn J, Breteler MM (2004) Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke 35(5):1057–1060
Duan GM, Guo L, Yang LX, Cui JB, Bi XM, Hao H, Yan JY, Li BJ, Zhou L, Liang XC (2009) Study on the association of apolipoprotein E-gene polymorphism with demented patients. J Henan Med Coll Staff Work 21:559–561
Engelborghs S, Dermaut B, Goeman J, Saerens J, Marien P, Pickut BA, Van den Broeck M, Serneels S, Cruts M, Van Broeckhoven C, De Deyn PP (2003) Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects. J Neurol Neurosurg Psychiatry 74(8):1148–1151
Fan P, Liu Y, Zhang ZH, Liu BW, Ge W, Ye SL, Cheng YM, Chen JJ (2001) Serum Apolipoprotein AΙ, B100 and E Levels and Apolipoprotein E polymorphism in patients with Alzheimer’s disease and multiple infarction dementia in Chinese population. JWCUMS 32:389–391
Group N (2001) Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet 357(9251):169–175
Hill J, Fillit H, Shah SN, del Valle MC, Futterman R (2005) Patterns of healthcare utilization and costs for vascular dementia in a community-dwelling population. J Alzheimers Dis 8(1):43–50
Huang Y (2006) Molecular and cellular mechanisms of apolipoprotein E4 neurotoxicity and potential therapeutic strategies. Curr Opin Drug Discov Dev 9(5):627–641
Jia JP, Zhang J, Xu M, Zhou WD (2002) Association between the apolipoprotein E gene polymorphism and the genetic sensitivity of sporadic Alzheimer’s disease. Chin J Geriatr 21:248–250
Jiang SD, Feng GY, Wu XD, Lin SC, Gu NF, Jin TG, Kang WM, Gao ZS, Ren DM, Jiang DK (1996) An analysis of association of apolipoprotein E allele ε4 with Alzheimer’s disease. Chin J Psychiatry 29:15–18
Jiang WY, Lv ZP, Qing L, Hu CY, Pang GF, Yang Z, Wei Y, Lv Y (2010) Correlation between apolipoprotein E gene polymorphisms and Alzheimer’s disease and vascular dementia. J Clin Neurol 23:408–410
Jones EL, Kalaria RN, Sharp SI, O’Brien JT, Francis PT, Ballard CG (2011) Genetic associations of autopsy-confirmed vascular dementia subtypes. Dement Geriatr Cogn Disord 31(4):247–253
Kalman J, Juhasz A, Csaszar A, Kanka A, Rimanoczy A, Janka Z, Rasko I (1998) Increased apolipoprotein E4 allele frequency is associated with vascular dementia in the Hungarian population. Acta Neurol Scand 98(3):166–168
Katzman R, Zhang MY, Chen PJ, Gu N, Jiang S, Saitoh T, Chen X, Klauber M, Thomas RG, Liu WT, Yu ES (1997) Effects of apolipoprotein E on dementia and aging in the Shanghai survey of dementia. Neurology 49(3):779–785
Kim KW, Youn JC, Han MK, Paik NJ, Lee TJ, Park JH, Lee SB, Choo IH, Lee DY, Jhoo JH, Woo JI (2008) Lack of association between apolipoprotein E polymorphism and vascular dementia in Koreans. J Geriatr Psychiatry Neurol 21(1):12–17
Knopman DS, Rocca WA, Cha RH, Edland SD, Kokmen E (2003) Survival study of vascular dementia in Rochester, Minnesota. Arch Neurol 60(1):85–90
Li RG, Zhao MX, Zuo L, Liu F (2009) The relationship between the forth exons of ApoE gene Polymorphism and vascular dementia. Contemp Med 15:71–72
Lin XJ, Hu CL, Xie YL, Zhang X, Liu XP, Yan G (2002) The relation between polymorphism of Apolipoprotein E Gene and vascular dementia. Chin J Neuroimmunol Neurol 9:17–20
Lu HY, Tian GL, Wang JH, Ning XJ, Tu J (2003) The relationship between gene polymorphism of apolipoprotein E and vascular dementia. Mod J Neurol Neurosurg 3:351–354
Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240(4852):622–630
Miyata M, Smith JD (1996) Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet 14(1):55–61
Mori T, Kobayashi M, Town T, Fujita SC, Asano T (2003) Increased vulnerability to focal ischemic brain injury in human apolipoprotein E4 knock-in mice. J Neuropathol Exp Neurol 62(3):280–291
Munafo MR, Flint J (2004) Meta-analysis of genetic association studies. Trends Genet 20(9):439–444
Nakayama S, Kuzuhara S (1999) Apolipoprotein E phenotypes in healthy normal controls and demented subjects with Alzheimer’s disease and vascular dementia in Mie Prefecture of Japan. Psychiatry Clin Neurosci 53(6):643–648
Nathan BP, Bellosta S, Sanan DA, Weisgraber KH, Mahley RW, Pitas RE (1994) Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science 264(5160):850–852
Niu WQ, Qi Y (2011) Meta-based evidence for apolipoprotein E varepsilon2/varepsilon3/varepsilon4 polymorphism in association with hypertension among Chinese. J Hum Hypertens (Epub ahead of print). doi:10.1038/jhh.2010.116
Niu W, Qi Y, Qian Y, Gao P, Zhu D (2009) The relationship between apolipoprotein E epsilon2/epsilon3/epsilon4 polymorphisms and hypertension: a meta-analysis of six studies comprising 1812 cases and 1762 controls. Hypertens Res 32(12):1060–1066
Peng DT, Xu XH, Feng Y, Zhu JY (2001) Apolipoprotein E 4 gene is a risk factor for Alzheimer’s disease. Chin J Intern Med 40:688–690
Roman GC (2002a) Vascular dementia may be the most common form of dementia in the elderly. J Neurol Sci 203–204:7–10
Roman GC (2002b) Vascular dementia revisited: diagnosis, pathogenesis, treatment, and prevention. Med Clin North Am 86(3):477–499
Roman GC (2005) Vascular dementia prevention: a risk factor analysis. Cerebrovasc Dis 20 (Suppl 2):91–100
Rubinsztein DC, Easton DF (1999) Apolipoprotein E genetic variation and Alzheimer’s disease. A meta-analysis. Dement Geriatr Cogn Disord 10(3):199–209 [published erratum appears in Dement Geriatr Cogn Disord 11 (4):238]
Saunders AM, Schmader K, Breitner JC, Benson MD, Brown WT, Goldfarb L, Goldgaber D, Manwaring MG, Szymanski MH, McCown N et al (1993) Apolipoprotein E epsilon 4 allele distributions in late-onset Alzheimer’s disease and in other amyloid-forming diseases. Lancet 342(8873):710–711
Slooter AJ, Tang MX, van Duijn CM, Stern Y, Ott A, Bell K, Breteler MM, Van Broeckhoven C, Tatemichi TK, Tycko B, Hofman A, Mayeux R (1997) Apolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation. JAMA 277(10):818–821
Song Y, Stampfer MJ, Liu S (2004) Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med 141(2):137–147
Stengard JH, Pekkanen J, Sulkava R, Ehnholm C, Erkinjuntti T, Nissinen A (1995) Apolipoprotein E polymorphism, Alzheimer’s disease and vascular dementia among elderly Finnish men. Acta Neurol Scand 92(4):297–298
Su J, Liu FJ, Chang GF (2005) Relationship between vascular dementia and apolipoprotein E gene polymorphism: a case-control study. Chin J Clin Rehabil 9:184–186
Wang HK, Fung HC, Hsu WC, Wu YR, Lin JC, Ro LS, Chang KH, Hwu FJ, Hsu Y, Huang SY, Lee-Chen GJ, Chen CM (2006) Apolipoprotein E, angiotensin-converting enzyme and kallikrein gene polymorphisms and the risk of Alzheimer’s disease and vascular dementia. J Neural Transm 113(10):1499–1509
Wiederkehr S, Simard M, Fortin C, van Reekum R (2008) Validity of the clinical diagnostic criteria for vascular dementia: a critical review. Part II. J Neuropsychiatry Clin Neurosci 20(2):162–177
Xu X, Li J, Sheng W, Liu L (2008) Meta-analysis of genetic studies from journals published in China of ischemic stroke in the Han Chinese population. Cerebrovasc Dis 26(1):48–62
Yang JY, Yu FC, Wang Y, Wu L, Wang MY, Duan Y, Yang Y, Chen Y, Zhu M, Ye Y, Zhang Y, Li C, Wu X (2008) Study of the polymorphisms of APOE gene in Alzheimer disease and vascular dementia. Nerv Dis Mental Health 8:138–140
Zhang XQ, Xiao JS, Huang CY (1997) Relationship between apolipoprotein E gene polymorphism and vascular dementia. Chin J Med Genet 14:31–34
Zhang JG, Yang JG, Lin ZX, He L, Feng GY, Ma XY, Wang CF, Lu PF, Song SB, Dong XZ, St Clair D, Breen G (2001) Apolipoprotein E epsilon4 allele is a risk factor for late-onset Alzheimer’s disease and vascular dementia in Han Chinese. Int J Geriatr Psychiatry 16(4):438–439
Zhang W, Tan L, Jiang SD (2007) The association of Apolipoprotein E and amyloid-β protein precursor in Alzheimer’s disease. Chin J Gerontol 27:268–270
Zhou K, Yu SZ, Wang GJ (1998) An analysis of apolipoprotein E polymorphism in aged patients with vascular dementia and cerebral infarction. J Apoplexy Nerv Dis 15:280–282
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This study was supported by the National Natural Science Foundation of China (No. 30971018).
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Liu, X., Li, L., Liu, F. et al. ApoE gene polymorphism and vascular dementia in Chinese population: a meta-analysis. J Neural Transm 119, 387–394 (2012). https://doi.org/10.1007/s00702-011-0714-6
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DOI: https://doi.org/10.1007/s00702-011-0714-6