Effect of factor XIII levels and polymorphisms on the risk of myocardial infarction in young patients

Balogh, László; Katona, Éva; Mezei, J. Zs.; Kállai, Judit; Gindele, Réka; Édes, István; Muszbek, László; Papp, Zoltán; Bereczky, Zsuzsanna

doi:10.1007/s11010-018-3326-8

Cited by 13 publications

(14 citation statements)

References 43 publications

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“…This is the second study regarding FXIII activity in MI in young patients. A recently published study revealed significantly elevated FXIII activity in very young patients below 40 years of age, but the increase was limited to patients with STEMI [15]. Our study included patients with STEMI and NSTEMI.…”

Section: Discussionmentioning

confidence: 98%

Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients

Ambroziak

Kuryłowicz

Budaj

2019

J Thromb Thrombolysis

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The aim of the study was to investigate the possible role of coagulation factor XIII (FXIII) plasma activity and its gene (F13A1) Val34Leu variant as well as thrombospondin-2 gene (THBS2) T/G 3′UTR and thrombospondin-4 gene (THBS4) Ala387Pro variants in the development of myocardial infarction (MI) in young patients. The studied group consisted of 158 patients aged < 50 years with MI, and the control groups consisted of 150 healthy people aged < 50 years and 202 patients suffering from MI aged ≥ 50 years. Factor XIII activity was measured by photometric assay; genetic variants were determined using the restriction fragment length polymorphism (RFLP) method. FXIII activity was significantly higher in the young MI group compared with young healthy controls and the MI ≥ 50 group (126.2 U/dl vs. 109.6 U/dl, p < 0.0001; 126.2 U/dl vs. 119.8 U/dl, p = 0.01, respectively). FXIII activity did not correlate with F13A1 gene variants. F13A1, THBS2 and THBS4 genotypes were equally distributed in all studied groups. There was also no statistically significant differences in the prevalence of the extended CC/TT/GG haplotype of F13A1/THBS2/THBS4 variants between the young MI group and the young healthy control group and between the young MI group and the MI aged ≥ 50 group. In conclusion, our study revealed that increased FXIII activity is associated with an increased risk of MI in young patients. None of studied single genetic variants—F13A1 Val34Leu, THBS2 T/G 3′UTR and THBS4 Ala387Pro—and the extended CC/TT/GG haplotype of F13A1/THBS2/THBS4 genes was associated with MI in young age.

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Section: Discussionmentioning

confidence: 98%

Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients

Ambroziak

Kuryłowicz

Budaj

2019

J Thromb Thrombolysis

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“…Decreased FXIII levels were associated with the minor allele carriers at rs6003. (61,62) The negative association of the clot density with ALT was strongest in the participants who inherited the minor G allele. FXIII clearly plays a role in modulating clot structure by increasing the stability of the brin clot by altering its structure and increasing bre density.…”

Section: Discussionmentioning

confidence: 99%

The association of alcohol with circulating total fibrinogen and plasma clot density is mediated by fibrinogen and FXIII genotypes

Rautenbach

Nienaber-Rousseau

Pieters

2020

Preprint

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Background Alcohol consumption is associated with haemostasis and so may influence cardiovascular conditions. It is unknown whether the association of alcohol with total and γ’ fibrinogen concentrations, as well as clot structure, are modulated by fibrinogen and factor (F)XIII single nucleotide polymorphisms (SNPs). Methods Total fibrinogen, γ’ fibrinogen and clot properties of 2010 healthy black South Africans were measured in relation to alcohol intake as well as its markers – gamma-glutamyltransferase (GGT), percentage carbohydrate deficient transferrin (%CDT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Fourteen fibrinogen and two SNPs in the FXIII gene were genotyped to determine their influence. Results Alcohol intake and its markers correlated negatively with fibrinogen and clot lysis time (CLT) as well as with most of the clot properties. Percentage γ’ fibrinogen correlated positively with AST and negatively with alcohol intake. We then stratified for alcohol intake and found inverse associations between γ’ fibrinogen and both %CDT and GGT–CDT in consumers, but the positive association with AST remained only in abstainers. Alcohol intake and its markers modulated the influence of fibrinogen SNPs on total fibrinogen concentrations and the fibrinogen SNPs as well as an FXIII SNP on clot density (all p <0.004). Conclusion/s We show for the first time that some individuals harbour certain genotypes that, in combination with alcohol consumption, might predispose or protect them from haemostatic factors that might lead to the development of cardiovascular disease. Studies are needed to clarify the mechanisms related to the interplay between alcohol and gene variants observed here.

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“…In a short-term survival study, we recently demonstrated that after AMI, Factor XIIIA (FXIIIA) circulating levels are an independent predictor of major adverse cardiovascular events (MACE), in particular for heart failure (HF) and death [ 2 ]. On the contrary, the role of F13A1 gene variants in AMI onset, recurrence, and in post-AMI outcomes is still controversial, including gender disparities [ 3 , 4 , 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

F13A1 Gene Variant (V34L) and Residual Circulating FXIIIA Levels Predict Short- and Long-Term Mortality in Acute Myocardial Infarction after Coronary Angioplasty

Ansani

Marchesini

Pestelli

et al. 2018

IJMS

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Factor XIIIA (FXIIIA) levels are independent predictors of early prognosis after acute myocardial infarction (AMI) and the Valine-to-Leucine (V34L) single nucleotide polymorphism (SNP) seems associated with lower AMI risk. Since the long-term AMI prognosis merits deeper investigation, we performed an observational study evaluating relationships between FXIIIA residual levels, cardiovascular risk-factors, and inherited genetic predispositions. FXIIIA V34L was genotyped in 333 AMI patients and a five-year follow-up was performed. FXIIIA levels assessed at day-zero (d0) and four days after AMI (d4), and conventional risk factors were analyzed, focusing on the development of major adverse cardiovascular events (MACE). FXIIIA assessed at d0 and d4 was also an independent MACE predictor in the long-term follow-up (FXIIIAd0, Odds Ratio (OR) = 3.02, 1.79–5.1, p = 0.013; FXIIIAd4, OR = 4.46, 2.33–8.55, p = 0.0001). FXIIIAd4 showed the strongest MACE association, suggesting that the FXIIIA protective role is maximized when high levels are maintained for longer time. Conversely, FXIIIA levels stratified by V34L predicted MACE at a lesser extent among L34-carriers (Hazard Risk (HR)VV34 = 3.89, 2.19–6.87, p = 0.000003; HRL34-carriers = 2.78, 1.39–5.57, p = 0.0039), and V34L did not predict all MACE, only multiple-MACE occurrence (p = 0.0087). Finally, in survival analysis, heart failure and death differed significantly from stroke and recurrent ischemia (p = 0.0013), with FXIIIA levels appreciably lower in the former (p = 0.05). Overall, genetically-determined FXIIIA levels have a significant long-term prognostic role, suggesting that a pharmacogenetics approach might help to select those AMI patients at risk of poor prognosis in the need of dedicated treatments.

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Effect of factor XIII levels and polymorphisms on the risk of myocardial infarction in young patients

Cited by 13 publications

References 43 publications

Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients

Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients

The association of alcohol with circulating total fibrinogen and plasma clot density is mediated by fibrinogen and FXIII genotypes

F13A1 Gene Variant (V34L) and Residual Circulating FXIIIA Levels Predict Short- and Long-Term Mortality in Acute Myocardial Infarction after Coronary Angioplasty

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