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Brain Trauma
Table 1 continued
Reference Gene Polymorphism Methodology Phenotype Results Comments
Corral et al., 2000
65
XIII Val34Leu 116 patients PICH Negative –
465 controls
Gemmati et al., 2001
62
XIII Val34Leu 130 patients PICH Positive OR 1.7, 95% CI 1.16–2.51; p=0.009
200 controls
Reiner et al., 2001
66
XIII Val34Leu 42 patients Women aged <45 Negative –
XIII Tyr204Phe 345 controls years with PICH Positive OR 2.09, 95% CI 1.1–7.5
XIII Pro564Leu Positive OR 4.3, 95% CI 1.4–1.7
PAI -675 4G/5G Negative –
Cho et al., 2002
79
XIII Val34Leu 58 patients PICH Negative –
48 controls
Endler et al., 2003
64
XIII Val34Leu 94 patients PICH Negative –
369 controls
Corral et al., 2001
63
F-V leiden Leiden 201 patients PICH Positive OR 0.19, 95% CI 0.03–0.95
F-II 20210A 201 controls Negative –
F-VII -323 D/I Positive OR 1.54, 95% CI 1.03–2.72
XIII Val34Leu Negative –
Greisenegger et al., 2007
73
F-VII -401G/T, -402 G/A 85 patients PICH Negative –
85 controls
Obach et al., 2006
70
Protein Z c.573-79G/A 156 patients PICH Negative –
147 controls
Munoz et al., 2007
74
GAS6 8 variants 199 patients PICH Negative –
150 controls
Li et al., 2003
72
MTHFR C677T 503 patients PICH Negative –
1,832 controls
McCarron et al., 2003
71
IL-1a (-899) C/T 42 patients CAA-related PICH Negative –
167 controls
Strand et al., 2007
49
OPG -1181G/C, -950T/C 61 patients PICH Positive -1181C/C genotype: OR 6.04,
773 controls 95% CI 1.71–21.29; p=0.005
IL-6 -174G/C Negative –
Strand et al., 2007
67
ESR1 c.454-397T/C 61 patients PICH Positive c.454-397T/T genotype: OR 3.94,
773 controls 95% CI 1.54–10.03
c.454-351A/G Negative –
Xu et al., 2008
69
PON2 C311S, G148A 150 patients PICH Negative –
120 controls
CAA = cerebral amyloid angiopathy; CI = confidence interval; OR = odds ratio; PICH = primary intracranial haemorrhage; IL = interleukin.
ischaemic attacks, lacunar strokes and subcortical dementia. e4 allele increases Aβ deposition in the cerebral vasculature in a dose-
Magnetic resonance imaging reveals extensive peri-ventricular white dependent manner.
35,36
The ε2 allele is associated with vasculopathic
matter leucoencephalopathy and the presence of microbleeds, changes in amyloid-laden vessels and rupture.
33
It has also been
predominantly in subcortical areas and the thalamus, detected on documented that ε2 and ε4 alleles of the ApoE gene are risk factors for
T2-weighted gradient echo imaging. Microbleeds can be present in the occurrence of lobar PICH, probably due to the presence of cerebral
31–69% of patients with CADASIL.
30
It was found that PICH can occur amyloid angiopathy in the carriers of these alleles.
2
In addition, the e4
in 25% of symptomatic patients with CADASIL, and this is closely allele was associated with earlier age at onset of CAA-related PICH
37
and
related to the number of cerebral microbleeds.
31
with warfarin-related PICH.
38
ε2 and ε4 allele carriers are also at
increased risk of recurrent haemorrhage compared with ε3 carriers.
39
Moreover, the presence of the e4 allele was linked to poor outcome of
It was found that primary intracerebral
PICH patients.
40
However, other studies did not find any association
between ApoE polymorphism and PICH.
41–45
In a recent meta-analysis,
haemorrhage can occur in 25% of
the ε2 allele was found to be an independent risk factor for PICH (odds
symptomatic patients with CADASIL, and
ratio [OR] 1.32, 95% confidence interval [CI] 1.01–1.74), whereas ε4
genotypes were not (OR 1.16, 95% CI 0.93–1.44).
46
this is closely related to the number of
cerebral microbleeds.
VKORC1 Gene
An interesting association between a haplotype in the vitamin K
epoxidase reductase complex subunit 1 (VKORC1) gene and arterial
Genetic Association Studies vascular diseases including PICH (OR 1.53, 95% CI 1.09–2.16; p<0.05)
Apolipoprotein E has been reported.
47
VKORC1 is implicated in haemostatic processes
Apolipoprotein E (ApoE) is a glycoprotein involved in cholesterol through γ-carboxylation of vitamin-K-dependent proteins. Common
transport and has three isoforms: ε2, ε3 and ε4. Accumulating evidence polymorphisms of VKORC1 gene have also been found to affect
implicates ApoE ε2/ε3/ε4 polymorphism with CAA-related PICH.
32–34
The interindividual differences in warfarin sensitivity.
46 EUROPEAN NEUROLOGICAL REVIEW