Blood coagulation factor XIII-A subunit Val34Leu polymorphisms and intracerebral hemorrhage risk: A meta-analysis of case-control studies.

BACKGROUND: Previous studies investigating the association between factor XIII-A subunit (FXIII-A) Val34Leu polymorphisms and intracerebral hemorrhage (ICH) had provided inconsistent results and no large systematic review or meta-analysis had been conducted regarding this issue.

METHODS: We conducted a meta-analysis to confirm whether the FXIII-A Val34Leu polymorphisms increased the risk of ICH. Relevant studies were identified from the Pubmed, Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases published up to September 2013. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for FXIII-A Val34Leu polymorphisms and ICH were calculated in a fixed-effects model or a random-effects model when appropriate. We also carried out the stratified analyses and sensitivity analyses by region, source of control group, and sample size.

RESULTS: Eight eligible studies were reviewed. As FXIII Val34Leu was absent or had a very low prevalence among East Asians, only six studies in Caucasians were analyzed, involving 564 cases and 1276 controls. Overall, the Leu allele of FXIII gene had a trend to slightly increased odds of having ICH, but there is no statistic significance (OR1.23, 95% CI 0.94-1.61, P = 0.13). The OR of genotypes Leu+(Leu/Leu or Leu/Val) for the risk of ICH was 1.21, 95% CI 0.98-1.50, P = 0.08. And the OR of recessive model genotypes was 1.53, 95% CI 0.81-2.88, P = 0.19. There was no difference of the association between the Leu allele of FXIII gene and risk of ICH in stratified analysis.

CONCLUSIONS: Our meta-analysis suggests that there is no evidence for strong association between FXIII Val34Leu polymorphisms and ICH, but Leu allele of FXIII gene might slightly increase the risk of ICH in Caucasians. Since limited studies and subjects were included, larger scale association studies exploring the gene-gene interactions and gene-environment interactions are necessary to further validate the association.