scholarly journals Association of Fibrinogen and Plasmin Inhibitor, but not Coagulation Factor XIII Gene Polymorphisms with Coronary Artery Disease

2020 ◽  
Author(s):  
Ana Bronic ◽  
Goran Ferencak ◽  
Robert Bernat ◽  
Jasna Lenicek Krleza ◽  
Jerka Dumic ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Factor Xiii ◽  
Active Form ◽  
Coagulation Factor ◽  
Rflp Analysis ◽  
Chain Gene ◽  
Nucleotide Polymorphisms ◽  
Artery Disease ◽  
Plasmin Inhibitor

Background: In the final phase of cloth formation, fibri(noge)n constitutes frame whereas factor XIII (FXIII) active form is responsible for the covalent cross-linking of fibrin fibers and plasmin inhibitor (PI), thus contributing to clot stability. It could be expected that any change of coagulation factors’ structure affects the clot formation and modulate the atherothrombotic risk. The aim was to determine the frequency of four single nucleotide polymorphisms: (i) A>G in codon 312 of the fibrinogen α-chain gene (rs6050, Thr312Ala FGA), (ii) C>T at position 10034 of the 3´untranslated region in the fibrinogen γ-chain gene (rs2066865, 10034C>T FGG), (iii) C>T in codon 564 of the FXIII-A subunit gene (rs5982, Pro564Leu FXIII-A), and (iv) C>T in codon 6 of the plasmin inhibitor gene (rs2070863, Arg6Trp PI) in Croatian patients and their association with coronary artery disease (CAD). Methods: We performed the unrelated case-control association study on the consecutive sample of patients ≥18 years old, who had undergone coronary angiography for investigation of chest pain and suspected CAD. Cases were patients with confirmed CAD (N=201) and controls were the subjects with no CAD (N=119). Samples were genotyped using PCR-RFLP analysis. Results: Observed frequencies of the rare alleles of Thr312Ala FGA, 10034C>T FGG, Leu564Pro FXIII-A and Arg6Trp PI polymorphisms were 21%, 17%, 14%, 20%, respectively. Patients with 10034C> T FGG CC genotype had 3.5 times (95% CI 1.02-12.03) higher adjusted odds for CAD than patients with 10034C> T FGG TT genotype. Patients with Arg6Trp PI CC genotype had 3.86 times (95% CI 1.23-12.12) higher odds for CAD than patients with Arg6Trp PI TT genotype. No difference was observed regarding any other investigated polymorphism, Conclusion: Our finding suggests that 10034C>T FGG and Arg6Trp PI are associated with CAD.

Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor VIII activity and independently from lipid profile

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5688-5697 ◽  
Author(s):  
Nicola Martinelli ◽  
Domenico Girelli ◽  
Barbara Lunghi ◽  
Mirko Pinotti ◽  
Giovanna Marchetti ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Factor Viii ◽  
Lipid Profile ◽  
Plasma Lipids ◽  
Density Lipoprotein ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Nucleotide Polymorphisms ◽  
Artery Disease

Abstract High levels of coagulation factor VIII (FVIII) have been associated with cardiovascular disease. Low-density lipoprotein receptor (LDLR) has been recently demonstrated to contribute to FVIII clearance from plasma. The aim of this study was to evaluate 3 single nucleotide polymorphisms in SMARCA4-LDLR gene locus (rs1122608, rs2228671, and rs688) and FVIII coagulant activity (FVIII:c) in subjects with (n = 692) or without (n = 291) angiographically confirmed coronary artery disease (CAD). High FVIII:c levels were an independent risk factor for CAD. The rs688 and rs2228671 genotypes were predictors of FVIII:c with T alleles associated with higher FVIII:c levels. The rs2228671T allele was associated also with reduced total and LDL-cholesterol levels. With respect to the risk of CAD, no association was found for rs2228671. Consistently with higher FVIII:c levels, the rs688T allele was associated with CAD, whereas, consistently with a favorable lipid profile, the rs1122608T allele was associated with a decreased CAD prevalence. After adjustment for classic cardiovascular risk factors, including plasma lipids, rs688 remained associated with CAD (OR for T carriers: 1.67 with 95% confidence interval, 1.10-2.54). Haplotype analysis confirmed such results. Our data suggest that polymorphisms at LDLR locus modulate FVIII:c levels and may be associated with CAD risk independently from plasma lipids.

Prevalence of Three Common Polymorphisms in the A-subunit Gene of Factor XIII in Patients with Coronary Artery Disease

1999 ◽  
Vol 81 (04) ◽  
pp. 511-515 ◽  
Author(s):  
H.P. Kohler ◽  
T.S. Futers ◽  
P.J. Grant
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Subunit Gene ◽  
Coding Region ◽  
Exon 2 ◽  
A Subunit ◽  
Artery Disease ◽  
Fxiii Activity

SummaryActivated blood coagulation factor XIII has an important role in the final stage of the clotting cascade by the covalent crosslinking of α- and γ-fibrin chains. We have recently shown that a functional polymorphism in exon 2, codon 34 of the FXIII A-subunit gene is protective against myocardial infarction. To investigate the prevalence of three other common point mutations in the A-subunit gene (codon 564, C to T, 650 G to A and 651 G to C) and their association with FXIII activity and antigen levels, 275 patients with coronary artery disease and 196 controls were studied. There was no difference in the prevalence of the polymorphisms between patients and controls or between patients with or without MI. Only genotype at codon 564 was associated with FXIII activity with lower activities in subjects possessing the T allele. There was evidence of linkage disequilibrium between codon 34 and codon 564. These results suggest that FXIIIVal34Leu is the only common polymorphism in the coding region of the A-subunit gene of FXIII associated with coronary artery disease.

scholarly journals Genetic and epigenetic associations of ANRIL with coronary artery disease and risk factors

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Bayi Xu ◽  
Zhixia Xu ◽  
Yequn Chen ◽  
Nan Lu ◽  
Zhouwu Shu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Dna Methylation ◽  
Coronary Artery ◽  
Gene Dosage ◽  
Density Lipoprotein ◽  
Nucleotide Polymorphisms ◽  
Coronary Syndrome ◽  
Non Coding Rna ◽  
Artery Disease

Abstract Background Both DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear. Methods Eighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case–control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14ARF, p15INK4b and p16INK4a) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100). Results Polymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p < 0.05). The incidence of CAD, multi-vessel disease, and modified Gensini scores demonstrated a strong, direct association with ANRIL gene dosage (p < 0.05). There was no significant association between ANRIL polymorphisms and myocardial infarction/acute coronary syndrome (MI/ACS) (p > 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = − 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype. Conclusions These results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.

Association of γA/γ’ Fibrinogen Levels and Coronary Artery Disease

2002 ◽  
Vol 88 (07) ◽  
pp. 26-31 ◽  
Author(s):  
Rehana Lovely ◽  
Lisa Falls ◽  
Hamid Al-Mondhiry ◽  
Charles Chambers ◽  
Gary Sexton ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Binding Site ◽  
Factor Xiii ◽  
Blood Donors ◽  
Human Populations ◽  
Total Plasma ◽  
Artery Disease

SummaryγA/γ’ fibrinogen is a fibrinogen isoform that constitutes about 15% of total plasma fibrinogen. This isoform contains an additional binding site for zymogen factor XIII and for active thrombin, and forms fibrin clots that are resistant to fibrinolysis in vitro. Little is known about the variability of γA/γ’ fibrinogen levels in human populations, whereas total fibrinogen levels are known to increase with age and are higher in women than in men. In this report, evidence is presented that, in contrast to total fibrinogen levels, γA/γ’ fibrinogen levels showed no significant association with age or gender in a population of normal blood donors. A study of γA/γ’ fibrinogen levels in patients undergoing coronary angiography also showed that γA/γ’ fibrinogen levels were higher on average in coronary artery disease patients than in patients without coronary artery disease, and that this association was independent of total fibrinogen levels.

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