ASSOCIATION OF A LYMPHOTOXIN-α VARIABLE SITE rs1041981 WITH DEVELOPMENT OF LONG-TERM UNFAVORABLE OUTCOMES IN PATIENTS WITH ACUTE CORONARY SYNDROME WITHOUT ST-SEGMENT ELEVATION

Lymphotoxin-α (LTA) is a major pro-inflammatory cytokine produced at the early stages of vascular inflammation, taking part in the formation of arterial atherosclerosis and development of coronary heart disease. Functional changes in the gene encoding LTA production may influence the development of coronary heart disease with unfavorable progression. However, studies for associations between rs1041981 (C-804A) LTA gene variant and development of acute cerebrovascular accidents, myocardial infarction, and severity of coronary atherosclerosis have yielded contradictory results. The purpose of our study was to investigate an association of rs1041981 gene LTA with risk of adverse events within five years of follow-up in the patients with acute coronary syndrome without ST elevation ST (nonST-ACS). 178 patients with nonST-ACS from the Kemerovo Cardiology Center Registry were included into the study. Genotyping of rs1041981 site variable LTA gene was performed by TaqMan technique using an “iCycler iQ” device (BIO-RAD, USA). Results: we have found that the A allele and A/A genotype polymorphism in LTA gene (rs1041981) have been associated with development of adverse cardiovascular events over five years of observation (respective p levels were 0.02 and 0.036). In patients with A/A genotype, the rs1041981 polymorphism in LTA gene was associated with 3.8-fold increase in adverse cardiovascular events, compared to patients having A/C or C/C genotype. Carriage of A allele in LTA gene (rs1041981) doubles the risk of adverse cardiovascular events in patients with nonST-ACS at long observation terms. By means of Kaplan-Meier method, we have determined that survival to the first endpoint occurred more often in carriers of the genotype A/A of LTA gene (rs1041981). The A/A genotype of LTA gene (rs1041981) proved to be more significant (p = 0.016) for development of adverse outcomes, when combining the patients with A/C and C/C genotypes. One may draw a conclusion that A allele and A/A genotype of rs1041981 LTA polymorphism is associated with development of adverse cardiovascular events during the five-year period following the index event in patients with nonST-ACS.

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