Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients.
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ABSTRACT:
SUBMITTER: Ambroziak M
PROVIDER: S-EPMC6744381 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients.
Ambroziak M M Kuryłowicz A A Budaj A A
Journal of thrombosis and thrombolysis 20191001 3
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 ≥ ...[more]
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Project description:AIMS:Acute myocardial infarction (MI) is the major cause of chronic heart failure. The activity of blood coagulation factor XIII (FXIIIa) plays an important role in rodents as a healing factor after MI, whereas its role in healing and remodelling processes in humans remains unclear. We prospectively evaluated the relevance of FXIIIa after acute MI as a potential early prognostic marker for adequate healing. METHODS AND RESULTS:This monocentric prospective cohort study investigated cardiac remodelling in patients with ST-elevation MI and followed them up for 1 year. Serum FXIIIa was serially assessed during the first 9 days after MI and after 2, 6, and 12 months. Cardiac magnetic resonance imaging was performed within 4 days after MI (Scan 1), after 7 to 9 days (Scan 2), and after 12 months (Scan 3). The FXIII valine-to-leucine (V34L) single-nucleotide polymorphism rs5985 was genotyped. One hundred forty-six patients were investigated (mean age 58 ± 11 years, 13% women). Median FXIIIa was 118% (quartiles, 102-132%) and dropped to a trough on the second day after MI: 109% (98-109%; P < 0.001). FXIIIa recovered slowly over time, reaching the baseline level after 2 to 6 months and surpassed baseline levels only after 12 months: 124% (110-142%). The development of FXIIIa after MI was independent of the genotype. FXIIIa on Day 2 was strongly and inversely associated with the relative size of MI in Scan 1 (Spearman's ? = -0.31; P = 0.01) and Scan 3 (? = -0.39; P < 0.01) and positively associated with left ventricular ejection fraction: ? = 0.32 (P < 0.01) and ? = 0.24 (P = 0.04), respectively. CONCLUSIONS:FXIII activity after MI is highly dynamic, exhibiting a significant decline in the early healing period, with reconstitution 6 months later. Depressed FXIIIa early after MI predicted a greater size of MI and lower left ventricular ejection fraction after 1 year. The clinical relevance of these findings awaits to be tested in a randomized trial.
| S-EPMC7524135 | biostudies-literature
Project description:We identified 7 CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001). The inclusion criteria for enrolling patients were drawn from the Prospective Cardiovascular Munster study [http://www.ncbi.nlm.nih.gov/pubmed/3202078] and Framingham Heart Study [http://www.ncbi.nlm.nih.gov/pubmed/9737513]. In brief, patients aged between 20 and 75 years with coronary arterial disease with more than 50% stenosis, as proven by cardiac catheterization, and a history of hyperlipidemia with serum cholesterol level greater than 240 mg/dL or low-density lipoprotein greater than 155 mg/dL were enrolled. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from whole blood samples. 40 Samples.
2014-08-09 | E-GEOD-31276 | biostudies-arrayexpress
Project description:Factor XIII (FXIII) is necessary for cross linking of fibrin strands and generation of stable fibrin clot. FXIII Val34Leu is a common genetic single nucleotide polymorphism that has been associated with accelerated fibrin stabilization and reduced rate of fibrinolysis. The contribution of Val34Leu to long term risk of recurrent myocardial infarction (MI) in patients with coronary stenting has not been conclusively established. The objective of the study was to examine the effects of Val34Leu on fibrin generation, platelet aggregation, and long term clinical outcomes in patients with coronary artery disease treated with dual antiplatelet therapy. Patients with angiographically documented coronary artery disease who were treated with aspirin and clopidogrel were enrolled (n = 211). Light transmittance aggregometry and plasma fibrin clot formation using thrombelastography (TEG) were determined. Genotyping of Val34Leu was performed using Taqman assay. Clinical events during follow up were recorded. Homozygous carriers of 34 Leu variant had significantly shorter fibrin clot formation time as compared to wild type individuals (TEG K: 1.27 ± 0.3 vs. 1.68 ± 1.1 min, p = 0.011). The Val34Leu variant was associated with gene dose dependent increased risk of MI (log rank, p = 0.002) or occurrence of composite of MI and CV death (log rank, p = 0.005) with highest event rates observed in homozygous carriers of 34 Leu. In summary, FXIII Val34Leu polymorphism was associated with increased rate of fibrin stabilization in homozygous carriers of the variant and may increase risk of recurrent MI and death in patients with angiographically established coronary artery disease treated with dual antiplatelet therapy.
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Project description:Multidisciplinary research from the last few decades has revealed that Factor XIII subunit A (FXIII-A) is not only involved in blood coagulation, but may have roles in various diseases. Here, we aim to summarize data from studies involving patients with mutations in the F13A1 gene, performed in FXIII-A knock-out mice models, clinical and histological studies assessing correlations between diseases severity and FXIII-A levels, as well as from in vitro experiments. By providing a complex overview on its possible role in wound healing, chronic inflammatory bowel diseases, athe-rosclerosis, rheumatoid arthritis, chronic inflammatory lung diseases, chronic rhinosinusitis, solid tumors, hematological malignancies, and obesity, we also demonstrate how the field evolved from using FXIII-A as a marker to accept and understand its active role in inflammatory and malignant diseases.
| S-EPMC7867190 | biostudies-literature
Project description:BackgroundRecent genome-wide association (GWA) studies in Caucasians identified multiple single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). The associations of those SNPs with myocardial infarction (MI) have not been replicated in Asian populations. Among those previously identified SNPs, we selected nine (rs10953541, rs1122608, rs12190287, rs12413409, rs1412444, rs1746048, rs3798220, rs4977574, rs579459, in or near genes 7q22, LDLR, TCF21, CYP17A1, LIPA, CXCL12, LPA, CDKN2A, ABO, respectively) because of the relatively high minor allele frequencies in Chinese individuals and tested the associations of the SNPs with MI and MI related risk factors in Chinese population.Methods and resultsWe conducted a case-control association study on a cohort of 2365 MI patients and 2678 unrelated controls from the Chinese population. Genotyping of 9 SNPs were performed by the TaqMan Real Time PCR method. After age, sex, and BMI adjustment, we observed the SNPs rs12190287, rs12413409, rs1412444, rs1746048 and rs4977574, were significantly associated with MI in additive models and rs12190287, rs12413409, rs4977574 were significantly associated with phenotypes of MI at the same time. We also found three SNPs rs1122608, rs3798220 and rs579459 were significantly associated with risk factors of MI, although they had no association with MI in Chinese population.ConclusionResults of this study indicate that 5 SNPs were associated with MI and 3 SNPs were associated with associated with lipoprotein levels but not with MI in a Chinese population. The present study supports some CAD-related genes in Caucasian as important genes for MI in a Chinese population.
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Project description:ObjectiveAssociations between obesity-related polymorphisms and the metabolic syndrome in 485 young ( ≤ 45 Years) Asian Indian patients with acute myocardial infarction (AMI), and 300 matched controls were assessed.MethodsGenetic variants included the adiponectin 45T→G and 276G→T, LEPR K109R and Q223R, MC4R-associated C→T and FTO A→T polymorphisms.ResultsThe metabolic syndrome, as defined by NCEP ATP III and IDF criteria, was diagnosed in 61 and 60% of patients, respectively. No relationship was found between the obesity-associated polymorphisms and the metabolic syndrome, or between AMI patients and controls. The MC4R-associated TT genotype occurred more frequently in patients with lower triglyceride levels (p = 0.024), while the adiponectin 45 TT genotype occurred more commonly in patients with normal fasting glucose levels (p = 0.004). The LEPR Q223R TT genotype was associated with low high-density lipoprotein (HDL) cholesterol levels (p = 0.003).ConclusionThe metabolic syndrome occurs commonly in young Asian Indian patients with AMI. No relationship was found between any obesity-associated polymorphism and the metabolic syndrome. Particular genotypes may exert protective or disadvantageous effects on individual components of the metabolic syndrome.
| S-EPMC3736384 | biostudies-literature
Project description:We identified 7 CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001). The inclusion criteria for enrolling patients were drawn from the Prospective Cardiovascular Munster study [http://www.ncbi.nlm.nih.gov/pubmed/3202078] and Framingham Heart Study [http://www.ncbi.nlm.nih.gov/pubmed/9737513]. In brief, patients aged between 20 and 75 years with coronary arterial disease with more than 50% stenosis, as proven by cardiac catheterization, and a history of hyperlipidemia with serum cholesterol level greater than 240 mg/dL or low-density lipoprotein greater than 155 mg/dL were enrolled.
2014-08-09 | GSE31276 | GEO
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