Coagulation Factor XIII Val34Leu Polymorphism in the Prediction of Premature Cardiovascular Events—The Results of Two Meta-Analyses

Abstract

Background: Polymorphisms within the gene that encodes for coagulation factor XIII (FXIII) have been suggested to be involved in the pathogeneses of ischemic stroke (IS) and myocardial infarction (MI). The Val34Leu polymorphism is one of the most commonly analysed FXIII polymorphisms. However, studies on the role of the Val34Leu polymorphism in the aetiology of vascular diseases often show contradictory results. In the present meta-analysis, we aimed to pool data from available articles to assess the relationship between the FXIII Val34Leu polymorphism and the susceptibilities to IS of undetermined source and premature MI in patients aged below 55 years. Methods: We searched databases (PubMed, Embase, Google Scholar, SciELO, and Medline) using specific keywords (the last search was in January 2022). Eventually, 18 studies (627 cases and 1639 controls for IS; 2595 cases and 4255 controls for MI) met the inclusion criteria. Data were analysed using RevMan 5.4 and StatsDirect 3 link software. The relation between Val34Leu polymorphism and disease was analysed in five genetic models, i.e., dominant, recessive, additive, heterozygous, and allelic. Results: No relation between Val34Leu polymorphism and IS in young adults was observed in all analysed genetic models. For premature MI, significant pooled OR was found between the carrier state of the Leu allele (Val/Leu + Leu/Leu vs. Val/Val) and a lack of MI, suggesting its protective role (OR = 0.80 95%CI 0.64–0.99, p = 0.04). A similar finding was observed for the heterozygous model in MI (Val/Leu vs. Val/Val) (OR = 0.77 95%CI 0.61–0.98, p = 0.03). No relation was found for the recessive, additive, and allelic models in MI. Conclusions: In the population of young adults, no positive correlation was found between the FXIII Val34Leu polymorphism and IS of undetermined source in any of the analysed genetic models. In turn, the carrier state of the 34Leu allele as well as FXIII heterozygotes themselves were found to play a protective role in relation to premature MI.

Differential Role of Factor XIII in Acute Myocardial Infarction and Ischemic Stroke

“…In contrast, other meta-analyses have suggested that FXIIIA Val34Leu polymorphism is a protective factor for MI generally [ 66 ] and in Caucasians [ 67 ], which was also concluded by recent review articles on this controversial issue [ 68 , 69 ]. Two comprehensive meta-analyses have suggested that being a carrier of the Val34Leu allele and FXIII heterozygotes themselves are associated with a protective effect against premature MI [ 70 ]. Another meta-analysis claimed that the protective effect of the FXIII-A Val34Leu polymorphism could be significantly influenced by interactions between genes and environmental factors [ 71 ].…”

“…A meta-analysis of 8800 individuals found no conclusive evidence linking the FXIII-A Val34Leu polymorphism with IS [ 106 ]. In a different meta-analysis encompassing 627 cases and 1639 controls within the young adult population, no significant association was observed between the FXIII Val34Leu polymorphism and undetermined source IS in any of the genetic models analyzed [ 70 ]. In this line, others concluded that screening for the FXIII Val34Leu polymorphism would not contribute significantly to the risk prediction of cerebrovascular disease [ 68 ].…”

Molecular and Genetic Risk Factors for Forming Central Nervous System Damage during Perinatal Period in Preterm Infants. A Review

“…Исследования показали более высокую активность FXII у носителей Leu, в то время как гомозиготы по Val обнаруживают снижение активности этого фактора. Полиморфизм Val34Leu FXII также влияет на структуру фибринового сгустка, особенно в присутствии повышенных концентраций фибриногена, делая его намного более плотным [29]. Низкий уровень FXII у недоношенных детей может быть одним из факторов, способствующих относительно более высокой фибринолитической активности, связанной с риском ВЖК [2].…”