Association between Lymphotoxin Alpha (-252G/A and -804C/A) Gene Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis.

PURPOSE: Lymphotoxin-Alpha (LTA) is a mediator of inflammation which may be associated with the risk of ischemic stroke (IS). Polymorphisms (-252A/G and -804C/A) in the LTA gene have been found to be associated with IS with contradictory results. The present meta-analysis aimed to provide a comprehensive account of the association of (-252A/G and -804C/A) gene polymorphisms of LTA gene with susceptibility to IS.

METHODS: A literature search for eligible candidate gene studies published before April 20, 2015 was conducted in the PubMed, EMBASE, Trip database and Google Scholar. The following combinations of main keywords were used: ('Lymphotoxin-alpha' or 'LTA' or 'tumour necrosis factor beta' or 'TNF-beta') and ('Ischemic stroke or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Fixed or random effects models were used to estimate the strength of association through Odds ratios (ORs) and 95% confidence interval (CI).

RESULTS: Four case-control studies for LTA -252A/G gene polymorphism showed no significant association under; dominant (OR, 0.9; 95% CI; 0.8 to 1.0, P value 0.34), recessive (OR, 1.1; 95% CI; 0.9 to 1.3; P value 0.21) models, indicating that GG and AG genotypes may not possibly confer an increased susceptibility to IS as compared to AA genotype. For LTA -804C/A gene polymorphism, three casecontrol studies also showed no significant association under; dominant (OR, 0.5; 95% CI; 0.1 to 2.3; P value 0.44), recessive (OR, 0.8; 95% CI; 0.38 to 2.07, P value 0.79) models with IS risk.

CONCLUSION: Based on ethnicity stratification, our meta-analysis suggests that LTA -252A/G gene polymorphism is found to be significantly associated with the risk of IS in Caucasian population, but not in Asian population. However, LTA -804C/A gene polymorphism is not found to be associated with the susceptibility of IS in both Asian as well as in Caucasian population. Further well designed large sample size prospective studies are needed to confirm these findings.