Apolipoprotein E Gene Polymorphisms Are Risk Factors for Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis

Hao Nie, Yang Hu, Na Liu, Ping Zhang, Gai-gai Li, Yan-yan Li, Chao Pan, Hai-han Yu, Qian Wu, Guo-feng Wu, Zhou-ping Tang

Current Medical Science ›› 2019, Vol. 39 ›› Issue (1) : 111-117.

Current Medical Science ›› 2019, Vol. 39 ›› Issue (1) : 111-117. DOI: 10.1007/s11596-019-2007-5
Article

Apolipoprotein E Gene Polymorphisms Are Risk Factors for Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis

Author information +
History +

Abstract

Intracerebral hemorrhage (ICH) is a serious clinical disease with high morbidity, whose pathogenesis might be related to apolipoprotein E (APOE) gene polymorphisms. To comprehensively evaluate the risk factors for ICH occurrence, we performed a meta-analysis. We searched online databases to identify eligible studies based on the relationship between APOE genetic polymorphisms and ICH occurrence risk. Specific and pooled odds ratios (ORs) were calculated and by assessing small study bias, we drew the relationship between APOE polymorphisms and ICH risk. We included 15 eligible studies in our study containing a total of 1642 ICH samples and 5545 normal controls. The comparison of ɛ4 and ɛ3 APOE genotypes revealed that specific and pooled ORs showed a significantly increased odds ratio in ICH patients with the ɛ4 genotype, indicating that ɛ4 gene is a risk factor for ICH occurrence, and the heterogeneity is acceptable. Similarly, it was found that the ɛ2 genotype also contributed to the incidence rate of ICH. However, after the subgroup analysis by ethnicity, this APOE genetic polymorphism acted as a harmful factor only in white populations, but did not show an effect in Asian populations. It was suggested that both ε2 and ε4 APOE alleles were risk factors for ICH in general. They were risk factors in white populations only, neither had a detectable effect in Asian populations after subgroup analysing by ethnicity.

Keywords

intracerebral hemorrhage / apolipoprotein E / allele / genetic polymorphism / meta-analysis

Cite this article

Download citation ▾
Hao Nie, Yang Hu, Na Liu, Ping Zhang, Gai-gai Li, Yan-yan Li, Chao Pan, Hai-han Yu, Qian Wu, Guo-feng Wu, Zhou-ping Tang. Apolipoprotein E Gene Polymorphisms Are Risk Factors for Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis. Current Medical Science, 2019, 39(1): 111‒117 https://doi.org/10.1007/s11596-019-2007-5

References

[1]
BrownRD, WhisnantJP, SicksJD, et al.. Stroke incidence, prevalence, and survival: secular trends in Rochester, Minnesota, through 1989. Stroke, 1996, 27(3): 373-380
[2]
SturgeonJD, FolsomAR, LongstrethWJ, et al.. Risk factors for intracerebral hemorrhage in a pooled prospective study. Stroke, 2007, 38(10): 2718-2725
CrossRef Google scholar
[3]
MahleyRW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science, 1988, 240(4852): 622-630
CrossRef Google scholar
[4]
HattersDM, BudamaguntaMS, VossJC, et al.. Modulation of apolipoprotein E structure by domain interaction: differences in lipid–boud and lipid–free forms. J Biol Chem, 2005, 280(40): 34 288-34 295
CrossRef Google scholar
[5]
OphirG, AmariglioN, Jacob–HirschJ, et al.. Apolipoprotein E4 enhances brain inflammation by modulation of the NF–kappaB signaling cascade. Neurobiol Dis, 2005, 20(3): 709-718
CrossRef Google scholar
[6]
AtadzhanovM, MwabaMH, MukomenaPN, et al.. Association of the APOE, MTHFR and ACE Genes Polymorphisms and Stroke in Zambian Patients. Neurol Int, 2013, 5(4): e20
CrossRef Google scholar
[7]
BoumendjelS, KhodjaD, HamriA, et al.. Apolipoprotein E polymorphism and cerebral stroke. Ann Biol Clin (Paris), 2013, 71(1): 21-26
[8]
ChenYC, Lee–ChenGJ, WuYR, et al.. Analyses of interaction effect between apolipoprotein E polymorphism and alcohol use as well as cholesterol concentrations on spontaneous deep intracerebral hemorrhage in the Taiwan population. Clin Chim Acta, 2009, 408(1–2): 128-132
CrossRef Google scholar
[9]
ChowdhuryAH, YokoyamaT, KokuboY, et al.. Apolipoprotein E genetic polymorphism and stroke subtypes in a Bangladeshi hospital–based study. J Epidemiol, 2001, 11(3): 131-138
CrossRef Google scholar
[10]
DasS, KaulS, JyothyA, et al.. Association of APOE (E2, E3 and E4) gene variants and lipid levels in ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population. Neurosci Lett, 2016, 628: 136-141
CrossRef Google scholar
[11]
DuzenliS, PirimI, GepdiremenA, et al.. Apolipoprotein E polymorphism and stroke in a population from eastern Turkey. J Neurogenet, 2004, 18(1): 365-375
CrossRef Google scholar
[12]
GarciaC, PinhoEMT, RochaL, et al.. Cerebral hemorrhage and apoE. J Neurol, 1999, 246(9): 830-834
CrossRef Google scholar
[13]
KokuboY, ChowdhuryAH, DateC, et al.. Agedependent association of apolipoprotein E genotypes with stroke subtypes in a Japanese rural population. Stroke, 2000, 31(6): 1299-1306
CrossRef Google scholar
[14]
SeifertT, LechnerA, FloohE, et al.. Lack of association of lobar intracerebral hemorrhage with apolipoprotein E genotype in an unselected population. Cerebrovasc Dis, 2006, 21(4): 266-270
CrossRef Google scholar
[15]
TasdemirN, TamamY, ToprakR, et al.. Association of apolipoprotein E genotype and cerebrovascular disease risk factors in a Turkish population. Int J Neurosci, 2008, 118(8): 1109-1129
CrossRef Google scholar
[16]
WooD, DekaR, FalconeGJ, et al.. Apolipoprotein E, statins, and risk of intracerebral hemorrhage. Stroke, 2013, 44(11): 3013-3017
CrossRef Google scholar
[17]
ZhangR, WangX, LiuJ, et al.. Apolipoprotein E gene polymorphism and the risk of intracerebral hemorrhage in the Chinese population. Genet Test Mol Biomarkers, 2012, 16(1): 63-66
CrossRef Google scholar
[18]
MccarronMO, HoffmannKL, DelongDM, et al.. Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes. Neurology, 1999, 53(9): 2176-2179
CrossRef Google scholar
[19]
CattoAJ, MccormackLJ, MansfieldMW, et al.. Apolipoprotein E polymorphism in cerebrovascular disease. Acta Neurol Scand, 2000, 101(6): 399-404
CrossRef Google scholar
[20]
MisraUK, KalitaJ, SomarajanBI. Recurrent intracerebral hemorrhage in patients with hypertension is associated with APOE gene polymorphism: a preliminary study. J Stroke Cerebrovasc Dis, 2013, 22(6): 758-763
CrossRef Google scholar
[21]
CorderEH, SaundersAM, StrittmatterWJ, et al.. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 1993, 261(5123): 921-923
CrossRef Google scholar
[22]
CorderEH, SaundersAM, RischNJ, et al.. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet, 1994, 7(2): 180-184
CrossRef Google scholar
[23]
BartzokisG, LuPH, GeschwindDH, et al.. Apolipoprotein E affects both myelin breakdown and cognition: implications for age–related trajectories of decline into dementia. Biol Psychiatry, 2007, 62(12): 1380-1387
CrossRef Google scholar
[24]
KonialisC, SpengosK, IliopoulosP, et al.. The APOE E4 Allele Confers Increased Risk of Ischemic Stroke Among Greek Carriers. Adv Clin Exp Med, 2016, 25(3): 471-478
CrossRef Google scholar
[25]
FalconeGJ, RadmaneshF, BrouwersHB, et al.. APOE epsilon variants increase risk of warfarinrelated intracerebral hemorrhage. Neurology, 2014, 83(13): 1139-1146
CrossRef Google scholar
[26]
LeclercqPD, MurrayLS, SmithC, et al.. Cerebral amyloid angiopathy in traumatic brain injury: association with apolipoprotein E genotype. J Neurol Neurosurg Psychiatry, 2005, 76(2): 229-233
CrossRef Google scholar
[27]
GreenbergSM, VonsattelJP, SegalAZ, et al.. Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy. Neurology, 1998, 50(4): 961-965
CrossRef Google scholar
[28]
TolarM, KellerJN, ChanS, et al.. Truncated apolipoprotein E (ApoE) causes increased intracellular calcium and may mediate ApoE neurotoxicity. J Neurosci, 1999, 19(16): 7100-7110
CrossRef Google scholar
[29]
LynchJR, PinedaJA, MorganD, et al.. Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. Ann Neurol, 2002, 51(1): 113-117
CrossRef Google scholar
[30]
DavisSM, BroderickJ, HennericiM, et al.. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology, 2006, 66(8): 1175-1181
CrossRef Google scholar
[31]
LiaquatI, DunnLT, NicollJA, et al.. Effect of apolipoprotein E genotype on hematoma volume after trauma. J Neurosurg, 2002, 96(1): 90-96
CrossRef Google scholar
[32]
BiffiA, AndersonCD, JagiellaJM, et al.. APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study. Lancet Neurol, 2011, 10(8): 702-709
CrossRef Google scholar
[33]
AlbertsMJ, GraffagninoC, McclennyC, et al.. ApoE genotype and survival from intracerebral haemorrhage. Lancet, 1995, 346(8974): 575
CrossRef Google scholar
[34]
RaffeldMR, BiffiA, BatteyTW, et al.. APOE epsilon4 and lipid levels affect risk of recurrent nonlobar intracerebral hemorrhage. Neurology, 2015, 85(4): 349-356
CrossRef Google scholar

Accesses

Citations

Detail

Sections
Recommended

/