Full Length ArticleRegulation of plasma factor XIII levels in healthy individuals; a major impact by subunit B intron K c.1952Â +Â 144 CÂ >Â G polymorphism

- The regulation of plasma level of factor XIII has been only partially explored.
- Plasma factor XIII levels are influenced by age and fibrinogen concentration.
- FXIII-B intron K c.1952 + 144 C > G polymorphism is a major determinant of FXIII level.
- Regulatory factors might modify the risk of vascular diseases through FXIII levels.

BackgroundThe 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.ObjectivesTo 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.Methods268 healthy individuals were enrolled in the study. FXIII activity was measured by the ammonia release assay; FXIII-A2B2 and 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.ResultsAll 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.ConclusionsPlasma FXIII levels are subjected to multifactorial regulation, in which age, fibrinogen level and FXIII-B intron K polymorphism are major determinants.