Subarachnoid haemorrhage (SAH) is characterised by bleeding in the subarachnoid space in the brain. There are various polymorphisms in genes which are associated with this disease. We performed a systematic meta- analysis to investigate the relationship of APOE polymorphism on aSAH. A comprehensive literature search was done in the Pubmed database, Science Direct, Cochrane library and Google Scholar. The OR and 95% CI were evaluated for the gene and aSAH association using fixed and random effect models. Publication bias was assessed using Begg's funnel plot and Egger's regression test. All statistical evaluations were done using the software Review Manager 5.0 and Comprehensive Meta Analysis v2.2.023. A total of 9 studies were assessed on APOE polymorphism (1100 Cases, 2732 Control). Meta analysis results showed significant association in ε2/ ε2 versus ε3/ε3, ε2 versus ε3 genetic models and ε2 allele frequency. In subgroup analysis statistically significant association was observed in Asians in the genetic models ε2/ ε2 versus ε3/ε3, ε2/ε3 versus ε3/ε3, ε2 versus ε3 and also in ε2 allele frequency. However, in Caucasian population only ε2/ε2 versus ε3/ε3 genetic model showed significant association between APOE and risk of aSAH. In this meta-analysis study, the ε2/ε2 genotype is associated with increased risk of aSAH.
Background
Aneurysmal subarachnoid hemorrhage is a life- threatening condition with high rate of disability and mortality. Apolipoprotein E (
APOE
) and Factor XIIIA (
F13A
) genes are involved in the pathogenetic mechanism of aneurysmal subarachnoid haemorrhage (aSAH).
We evaluated the association of promoter methylation status of
APOE
and
F13A
gene and risk of aSAH.
Methods
For evaluating the effect of hypermethylation in the promoter region of these genes with risk of aSAH, we conducted a case -control study with 50 aSAH patients and 50 healthy control. The methylation pattern was analysed using methylation specific PCR. The risk factors associated with poor outcome after aSAH was also analysed in this study. The outcome was assessed using Glasgow outcome score (GOS) after 3 months from the initial bleed.
Results
The frequency of
APOE
and
F13A
methylation pattern showed insignificant association with risk of aSAH in this study. Gender stratification analysis suggests that
F13A
promoter methylation status was significantly associated with the risk of aSAH in male gender. Age, aneurysm located at the anterior communicating artery and diabetes mellitus showed significant association with poor outcome after aSAH.
Conclusion
There was no significant association with
APOE
promoter methylation with the risk as well as outcome of patients after aSAH.
F13A
promoter methylation status was significantly associated with risk of aSAH in male gender, with no significant association with outcome after aSAH.
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