Genotype/phenotype correlations for coagulation factor XIII: Specific normal polymorphisms are associated with high or low factor XIII specific activity

Factor XIII is a transglutaminase essential for normal hemostasis. We have studied the plasma FXIII levels and FXIII activity in 71 individuals and fo und these to be normally distributed. FXIII specific activity is also norma lly distributed. However, we show that FXIII activity is not directly depen dent on FXIII revels, and individuals with low FXIII levels may have high F XIII activity and vice versa. We have determined the FXIIIA genotype in the se individuals to assess whether the variation observed in FXIII specific a ctivity is dependent on specific polymorphisms in the FXIIIA gene. Our data show that the Leu34 and Leu564 variants give rise to increased FXIII speci fic activity, while the Phe204 variant results in lower FXIII specific acti vity. We also report preliminary evidence that the Phe204 polymorphism may be associated with recurrent miscarriage. Overall, we have identified 23 un ique FXIIIA genotypes. Certain specific FXIIIA genotypes consistently give rise to high, low, or median FXIII specific activity levels, while others a ppear to have little or no consistent influence on the FXIII phenotype. The se genotype to phenotype relationships are discussed in light of the growin g interest in the role of FXIII in clinical problems involving an increased thrombotic tendency. (C) 1999 by The American Society of Hematology.