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Factor XIII B subunit polymorphisms and the risk of coronary artery disease.

Mezei ZA, Bereczky Z, Katona É, Gindele R, Balogh E, Fiatal S, Balogh L, Czuriga I, Ádány R, Édes I, Muszbek L - Int J Mol Sci (2015)

Bottom Line: The p.His95Arg polymorphism did not influence the risk of CAS or MI.However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed.It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei Krt., Debrecen H-4032, Hungary. mezeiza@med.unideb.hu.

ABSTRACT
The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.

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The effect of FXIII-A Val34Leu, FXIII-B intron K nt29756 C>G polymorphisms and their combination on FXIII activity and antigen levels. FXIII levels adjusted for gender, smoking, serum total cholesterol and plasma fibrinogen levels are expressed as the mean ± SD; the numerical values of the means are also shown. The combination of FXIII-A and FXIII-B alleles are shown on the abscissa; Val34 and intron K C represent homozygosity for the wild-type FXIII-A and FXIII-B alleles; Leu34 and intron K G represent carriers of the respective mutant allele. Significant differences between genotype combinations are indicated by the p-values associated with the horizontal lines on the upper part of the figure. FXIII activity (A,C,E,G) and antigen (B,D,F,H) levels are demonstrated in the whole study group (A,B), in the CAS−MI− (C,D), in the CAS+ (E,F) and in the MI+ (G,H) patient groups.
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ijms-16-01143-f001: The effect of FXIII-A Val34Leu, FXIII-B intron K nt29756 C>G polymorphisms and their combination on FXIII activity and antigen levels. FXIII levels adjusted for gender, smoking, serum total cholesterol and plasma fibrinogen levels are expressed as the mean ± SD; the numerical values of the means are also shown. The combination of FXIII-A and FXIII-B alleles are shown on the abscissa; Val34 and intron K C represent homozygosity for the wild-type FXIII-A and FXIII-B alleles; Leu34 and intron K G represent carriers of the respective mutant allele. Significant differences between genotype combinations are indicated by the p-values associated with the horizontal lines on the upper part of the figure. FXIII activity (A,C,E,G) and antigen (B,D,F,H) levels are demonstrated in the whole study group (A,B), in the CAS−MI− (C,D), in the CAS+ (E,F) and in the MI+ (G,H) patient groups.

Mentions: The presence of intron K nt29756 G allele significantly decreased FXIII levels independently of its combination with FXIII-A Val34 homozygotes or Leu34 carriers in the whole study population (Figure 1A,B), as well as in the CAS+ group (Figure 1E,F). In MI+ patients, there was a similar tendency, but the extent of decrease in the FXIII levels was statistically significant only if intron K G and FXIII-A Leu34 carriership were combined (Figure 1G,H). As compared to patients homozygous for the FXIII-A Val34 allele and carrying the intron K nt29756 G allele, FXIII levels of patients carrying both FXIII-A Leu34 and intron K nt29756 G alleles were decreased, but the differences were not statistically significant.


Factor XIII B subunit polymorphisms and the risk of coronary artery disease.

Mezei ZA, Bereczky Z, Katona É, Gindele R, Balogh E, Fiatal S, Balogh L, Czuriga I, Ádány R, Édes I, Muszbek L - Int J Mol Sci (2015)

The effect of FXIII-A Val34Leu, FXIII-B intron K nt29756 C>G polymorphisms and their combination on FXIII activity and antigen levels. FXIII levels adjusted for gender, smoking, serum total cholesterol and plasma fibrinogen levels are expressed as the mean ± SD; the numerical values of the means are also shown. The combination of FXIII-A and FXIII-B alleles are shown on the abscissa; Val34 and intron K C represent homozygosity for the wild-type FXIII-A and FXIII-B alleles; Leu34 and intron K G represent carriers of the respective mutant allele. Significant differences between genotype combinations are indicated by the p-values associated with the horizontal lines on the upper part of the figure. FXIII activity (A,C,E,G) and antigen (B,D,F,H) levels are demonstrated in the whole study group (A,B), in the CAS−MI− (C,D), in the CAS+ (E,F) and in the MI+ (G,H) patient groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307295&req=5

ijms-16-01143-f001: The effect of FXIII-A Val34Leu, FXIII-B intron K nt29756 C>G polymorphisms and their combination on FXIII activity and antigen levels. FXIII levels adjusted for gender, smoking, serum total cholesterol and plasma fibrinogen levels are expressed as the mean ± SD; the numerical values of the means are also shown. The combination of FXIII-A and FXIII-B alleles are shown on the abscissa; Val34 and intron K C represent homozygosity for the wild-type FXIII-A and FXIII-B alleles; Leu34 and intron K G represent carriers of the respective mutant allele. Significant differences between genotype combinations are indicated by the p-values associated with the horizontal lines on the upper part of the figure. FXIII activity (A,C,E,G) and antigen (B,D,F,H) levels are demonstrated in the whole study group (A,B), in the CAS−MI− (C,D), in the CAS+ (E,F) and in the MI+ (G,H) patient groups.
Mentions: The presence of intron K nt29756 G allele significantly decreased FXIII levels independently of its combination with FXIII-A Val34 homozygotes or Leu34 carriers in the whole study population (Figure 1A,B), as well as in the CAS+ group (Figure 1E,F). In MI+ patients, there was a similar tendency, but the extent of decrease in the FXIII levels was statistically significant only if intron K G and FXIII-A Leu34 carriership were combined (Figure 1G,H). As compared to patients homozygous for the FXIII-A Val34 allele and carrying the intron K nt29756 G allele, FXIII levels of patients carrying both FXIII-A Leu34 and intron K nt29756 G alleles were decreased, but the differences were not statistically significant.

Bottom Line: The p.His95Arg polymorphism did not influence the risk of CAS or MI.However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed.It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei Krt., Debrecen H-4032, Hungary. mezeiza@med.unideb.hu.

ABSTRACT
The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.

Show MeSH
Related in: MedlinePlus