Risk for early pregnancy loss by factor XIII Val34Leu: the impact of fibrinogen concentration.
BACKGROUND
We have already described a significantly elevated overall risk for recurrent pregnancy loss (RPL) in women carrying the coagulation factor XIII (FXIII) Val34Leu and/or the plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism assuming that these polymorphisms contribute synergistically to RPL because of impaired hypofibrinolysis. Recent studies on FXIII indicate that the impact of the FXIII 34Leu genotype on fibrin structure and fibrinolysis is affected by fibrinogen concentration. Therefore, we reinvestigated the association between fibrinogen concentrations and FXIII Val34Leu with early RPL.


METHODS
In this case-control study, we enrolled 49 women with a history of two consecutive or three to six nonconsecutive pregnancy losses between the 8th and 12th week of gestation and 48 healthy controls. The risk for RPL in carriers of FXIII 34Leu at fibrinogen levels above or below the median and first tertile of controls was evaluated.


RESULTS
In carriers of the 34Leu allele, fibrinogen levels below the median (i.e., ≤ 300 mg/dl) and the first tertile (i.e., ≤ 284 mg/dl) of controls were associated with an increased risk for RPL [(2.9 (1.1-7.7), 3.9(1.0-15.0)].


CONCLUSIONS
The FXIII Val34Leu polymorphism may be associated with the development of early RPL in association with fibrinogen concentrations. At fibrinogen levels in the low normal range, FXIII 34Leu may modify fibrin structure toward an increased resistance to fibrinolysis.
Department of Laboratory Medicine, Rudolfstiftung Hospital, Vienna, Austria.
Astrid
A
Dossenbach-Glaninger
Mick
M
van Trotsenburg
Christian
C
Oberkanins
Johanna
J
Atamaniuk
D000026:Abortion, Habitual / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D005340:Fibrinogen; D005176:Factor XIII
coagulation; factor XIII; factor XIII Val34Leu polymorphism; fibrinogen; recurrent pregnancy loss