Regulation of plasma factor XIII levels in healthy individuals; a major impact by subunit B intron K c.1952+144 C>G polymorphism.
BACKGROUND
The regulation of plasma factor XIII (FXIII) levels in healthy individuals has been only partially explored. The identification of major non-genetic and genetic regulatory factors might provide important information on the contribution of FXIII to the risk of cardio/cerebrovascular diseases.


OBJECTIVE
To determine the effect of age, smoking, BMI, fibrinogen concentration on plasma FXIII activity, complex FXIII antigen (FXIII-A2B2) and total FXIII-B subunit (tFXIII-B) level, to correlate FXIII-B level with the other two FXIII parameters and to assess the variation of FXIII levels in carriers of major FXIII subunit polymorphisms.


METHODS
268 healthy individuals were enrolled in the study. FXIII activity was measured by the ammonia release assay; FXIII-A2B2and tFXIII-B were determined by ELISAs. FXIII-A p.Val34Leu, FXIII-B p.His95Arg and FXIII-B intron K c.1952+144 C>G polymorphisms were identified by RT-PCR using melting point analysis with fluorescence resonance energy transfer detection.


RESULTS
All investigated FXIII parameters showed significant positive correlation with age and fibrinogen level; gender and BMI influenced only tFXIII-B. A highly significant positive correlation was demonstrated between tFXIII-B and the other FXIII parameters. FXIII-A p.Val34Leu polymorphism had only slight, if any effect on FXIII levels. The FXIII-B Arg95 allele moderately increased all three FXIII parameters, but the effect became statistically significant only after adjustment. The FXIII-B intron K G allele drastically decreased FXIII levels, and it seemed to be in synergism with the FXIII-A Leu34 allele.


CONCLUSIONS
Plasma FXIII levels are subjected to multifactorial regulation, in which age, fibrinogen level and FXIII-B intron K polymorphism are major determinants.
Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Zoltán A
ZA
Mezei
Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Éva
É
Katona
Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Judit
J
Kállai
Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Zsuzsanna
Z
Bereczky
Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Éva
É
Molnár
Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of Medicine, Debrecen, Hungary; Borsod-Abaúj-Zemplén County Hospital and University Teaching Hospital, Miskolc, Hungary.
Bettina
B
Kovács
András Jósa Szabolcs-Szatmár-Bereg County Hospital and University Teaching Hospital, Nyíregyháza, Hungary.
Éva
É
Ajzner
Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Zsuzsa
Z
Bagoly
András Jósa Szabolcs-Szatmár-Bereg County Hospital and University Teaching Hospital, Nyíregyháza, Hungary.
Tünde
T
Miklós
Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of Medicine, Debrecen, Hungary; Vascular Biology, Thrombosis and Hemostasis Research Group of the Hungarian Academy of Sciences, University of Debrecen, Hungary. Electronic address: muszbek@med.unideb.hu.
László
L
Muszbek
D000328:Adult; D015992:Body Mass Index; D005176:Factor XIII / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D005340:Fibrinogen; D005176:Factor XIII; C054380:factor XIIIb
Factor XIII; Fibrinogen; Gender; Healthy volunteers; Polymorphism