Abstract
The risk of cerebral infarction (CI) is contributed to the combination of environmental influences and genetic factors. The Apolipoprotein E (APOE) gene polymorphism as a risk factor in CI has been suggested, but direct evidence from genetic association studies remains inconclusive even in Chinese population. The purpose of this study was to identify association between the APOE ε2/ε3/ε4 polymorphism and the development of CI. Published relevant case–control studies were collected from electronic databases. Data were combined using odds ratio (OR) with 95 % confidence interval (CI). Totally, 29 studies published from 1997 to 2012, involving 2,737 CI cases and 2,689 controls in Chinese population were subjected to final analysis. The pooled results suggested that CI subjects carrying ε4 allele had an increased risk for CI (ε4 vs. ε3: OR = 2.50, 95 % CI 1.98–3.16, P < 0.001, ε4 carriers vs. E3E3 genotype: OR = 2.82, 95 % CI 2.16–3.67, P < 0.001), compared with those carrying ε3 allele. However, carriers of APOE ε2 allele had no significant increased risk for CI, compared with those carrying ε3 allele. Potential publication bias was observed in the genetic model of ε4 versus ε3, but the results might not be affected deeply by the publication bias. Using the trim and fill method, the adjusted risk estimate for ε4 allele versus ε3 allele was attenuated but remained significant (OR = 2.00, 95 % CI 1.59–2.53, P < 0.001), suggesting the stability of our results. Taken together, our study suggests that APOE ε4 allele is associated with an increased risk of developing CI in Chinese population.
Similar content being viewed by others
References
Anthopoulos PG, Hamodrakas SJ, Bagos PG (2010) Apolipoprotein E polymorphisms and type 2 diabetes: a meta-analysis of 30 studies including 5423 cases and 8197 controls. Mol Genet Metab 100(3):283–291
Ashavaid TF, Todur SP, Nair KG (2003) Apolipoprotein E polymorphism and coronary heart disease. J Assoc Physicians India 51:784–788
Bazrgar M, Karimi M, Fathzadeh M, Senemar S, Peiravian F, Shojaee A, Saadat M (2008) Apolipoprotein E polymorphism in southern Iran: E4 allele in the lowest reported amounts. Mol Biol Rep 35(4):495–499
Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101
Cao W, Chen F, Teng L, Wang SZ, Fu SB, Zhang GY (1999) The relationship between Apolipoprotein E gene polymorphism and coronary heart disease and arteriosclerotic cerebral infarction. Chin J Med Genet 16(4):249–251
Deng K, Xiao ZJ, Wu XQ, Zhang Y (2011) The study on the apolipoprotein E gene polymorlJilism in different ages patients with lacunar infarction. Prev Treat Cardio-Cereb-Vasc Dis 11(1):15–18
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Ding J, Zhu WB, Fan W, Han QQ, Zhang JG, He L (2000) Study on the correlation of apolipoprotein E gene polymorphism and cerebral infarction. Chin J Nerv Ment Dis 26(6):371–372
Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Guo Y, Han SC (2002) Study on the relationship between apolipoprotein E gene polymorphism and atherosclerotic artery infarction in young people. J Apoplexy Nerv Dis 19(4):249
Hassan A, Markus HS (2000) Genetics and ischaemic stroke. Brain 123:1784–1812
Higgins JP, Thompson SE (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558
Huo Y, Gao XG, Teng ZP, Ren ZH, Pan KF (2006) Relationship between gene polymorphisms of angiotensin converting enzyme gene I/D, apolipoprotein E gene, β-fibrinogen 148C/T, N5, NC10-methylene-tetra-hydrofolic acid reductase 677C/T and cerebral infarction. Chin J Stroke 1(12):846–851
Jin ZQ, Fan YS, Ding J, Chen M, Fan W, Zhang GJ et al (2004) Association of apolipoprotein E 4 polymorphism with cerebral infarction in Chinese Han population. Acta Parmacol Sin 25(3):352–356
Kesäniemi YA, Ehnholm C, Miettinen TA (1987) Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. J Clin Invest 80(2):578–581
Lai CL, Liu CK, Lin RT, Tai CT (2007) Association of apolipoprotein E polymorphism with ischemic stroke subtypes in Taiwan. Kaohsiung J Med Sci 23:491–497
Li YW, He X, Zhang LX, Li F, Zhang DZ (2001) The relationship between polymorphisms of apolipoprotein E gene and cerebrovascular disorder. Prev Treat Cardio-Cereb Vasc Dis 1(3):17–19
Li ZH, Shen LH, Ke KF (2004) Genetic polymorphism of apolipoprotein E in patients with family aggregation or non-family aggregation of cerebral infarctio. Chin J Clin Rehabil 8(31):7064–7066
Liu LD, Cai YQ, Li SM, Chen SQ, Chen BM (2000) Study on the distribution of the polymorphisms of apolipoprotein E in patients with atherosclerotic cerebral infarction with PCR-RFLP. J Mod Clin Med Bioeng 6(4):250–251
Liu Y, Laakso MP, Karonen JO, Vanninen RL, Nuutinen J, Soimakallio S, Aronen HJ (2002) Apolipoprotein E polymorphism and acute ischemic stroke: a diffusion- and perfusion-weighted magnetic resonance imaging study. J Cereb Blood Flow Metab 22(11):1336–1342
Lu HY, Tian GL, Cheng Y, Tu J (2008) Analysis of apolipoprotein E gene polymorphism in three kinds of cerebral infarction. Tianjin Med J 36(10):759–761
Ma FY, Wu W, Wang F, Zhang Y, Lu XH (2006) Association of apolipoprotein E polymorphism with lipid metabolism and ischemic stroke subtypes. Chin J Geriatr Heart Brain Vessel Dis 8(8):513–516
Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240(4852):622–630
Mahley RW, Rall SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1:507–537
Man X, Yu BX, Pang ZY, Len ZP (2007) Study of the relationship between the polymorphism of apoE gene and cerebral infarction. Chin J Behav Med Sci 16(9):797–798
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748
McCarron MO, Delong D, Alberts MJ (1999) APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis. Neurology 53(6):1308–1311
Pablos-Méndez A, Mayeux R, Ngai C, Shea S, Berglund L (1997) Association of ApoE polymorphism with plasma lipid levels in a multiethnic elderly population. Arterioscler Thromb Vasc Biol 17:3534–3541
Paik YK, Chang DJ, Reardon CA, Davies GE, Mahley RW, Taylor JM (1985) Nucleotide sequence and structure of the human apolipoprotein E gene. Proc Natl Acad Sci USA 82:3445–3449
Shen LH, Ke KF, Li ZH, Pan M (2002) Research on apolipoprotein E gene polymorphism in patients with atherosclerotic cerebral infarction. Med J Commun 16(5):504–505
Su J, Tan L, Chang GF (2003) Study on the correlation between apolipoprotein E gene polymorphism and vascular dementia. Chin J Nerv Ment Dis 29(6):457–460
Sun HY, He JL, Yuan LH, Yang YM, Cheng JL (2008) Relationship of apolipoprotein E gene polymorphism with cerebral vascular disease. Med J West China 20(1):60–63
Tang LY, Wang XT, Yu K, Zhang HQ, Zheng JC, Tan YX (2007) Correlative analysis of apolipoprotein B, E gene polymorphism and several common diseases in southern area of Zhejiang province. J Wenzhou Med Coll 37(1):14–17
Um JY, Kim HM, Park HS, Joo JC, Kim KY, Kim YK, Hong SH (2005) Candidate genes of cerebral infarction and traditional classification in Koreans with cerebral infarction. Int J Neurosci 115(6):743–756
Wang TG, He ZY, Li YQ, Liu FP, Huang SS, Zhou TH (2000) The relation between Apolipoprotein E gene polymorphism and atherosclerotic cerebral infarction. Hereditas 22(1):4–6
Wang XT, Huang HJ, Yu K, Shen ZJ, Tan YX, Hu XX (2003) Apolipoprotein E gene polymorphism in people with cerebrovascular disease in south of Zhejiang province. Nerv Dis Ment Hyg 3(1):17–19
Wang XJ, Wang Y, Wang J (2009) Study on the relationship between apolipoprotein E gene polymorphism and cerebral infarction genetic susceptibility in the elderly population of Baoding. Chin J Clin (Electron Ed) 3(12):2021–2026
Xiao ZJ, Zhao SP, Nie S, Tan LM, Jiang B, Wu J (2005) The relationship between ApoE gene polymorphism and lipid parameters. Chin J Epidemiol 26(7):533–536
Xie DL, Xu H, Wang YM, Liu H (2008) Relationship between apolipoprotein E gene polymorphism and atherosclerotic cerebral infarction. J Clin Neurol 21(1):58–59
Xu LG, Li ZH (2002) Relationship between apolipoprotein E gene polymorphism and vascular dementia. J Clin Neurol 15(5):292–293
Yamagishi K, Iso H, Kitamura A, Sankai T, Tanigawa T, Naito Y, Sato S, Imano H, Ohira T, Shimamoto T (2003) Smoking raises the risk of total and ischemic strokes in hypertensive men. Hypertens Res 26:209–217
Yan SK, Zhou X, Li XL, Yu DL, Ha DW (1997) Relationship between gene polymorphism of apolipoprotein E and serum lipids, lipoproteins, and apolipoproteins in Chinese patients with atherothrombotic brain infarction. Chin J Neuroimmunol Neurol 4(1):16–21
Yang FB, Li XY, Mu JX (2010) Study on the relationship between apolipoprotein E gene polymorphism and vascular cognitive impairment. Chin J Integr Med Cardio/Cerebrovasc Dis 8(10):1194–1196
Yeh PS, Lin HJ, Li YH, Lin KC, Cheng TJ, Chang CY, Ke DS (2004) Prognosis of young ischemic stroke in Taiwan: impact of prothrombotic genetic polymorphisms. Thromb Haemost 92(3):583–589
Yu X, Shao XG, Tan L, Luo B (2000) Apolipoprotein E polymorphism and cerebral infarction. Acta Acad Med Qingdao Univ 36(4):265–267
Zhang X, Hao HJ, Yuan JM, Wang XT (2001) Early recurrent cerebral infarction and polymorphism of apolipoprotein E gene. Zhejiang Clin Med J 3(7):467–468
Zhou J, Yu FM, Li XX (2006) The relationship between apolipoprotein E gene polymorphism and cerebral infarction. Chin J Cerebrovasc Dis 3(6):263–266
Zhou ZY, Fu XN, Su QJ, Long DY, Chen ZB, Wang T (2009) Relationship of apoE gene polymorphism and cerebral infarction in Hainan Li nationality population. Chongqing Med J 38(22):2822–2824
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wang, Qy., Wang, Wj., Wu, L. et al. Meta-analysis of APOE ε2/ε3/ε4 polymorphism and cerebral infarction. J Neural Transm 120, 1479–1489 (2013). https://doi.org/10.1007/s00702-013-1019-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-013-1019-8