Which thrombophilic gene mutations are risk factors for recurrent pregnancy loss?
OBJECTIVE
Thrombophilia has been associated with poor obstetrical outcomes. To determine the association of specific inherited thrombophilias and recurrent pregnancy loss, 10 thrombophilic genes were investigated.


METHODS
A total of 550 women with a history of recurrent pregnancy loss had buccal swabs taken for DNA analyses of the following gene mutations: factor V G1691A, factor V H1299R (R2), factor V Y1702C, factor II prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C. The frequencies of these mutations were compared with controls published in the literature.


RESULTS
When examined individually, PAI-1 4G/5G (P = 0.009), factor XIII V34L (P < 0.0001), and homozygous MTHFR C667T (P < 0.0001) correlated significantly with recurrent pregnancy loss compared with controls. The frequency of the factor V Y1702C mutation was extremely low in patients and controls; thus, this gene was removed from further calculations. The remaining six mutated genes, when analyzed cumulatively, also corresponded with recurrent pregnancy loss (P < 0.0001).


CONCLUSIONS
A panel of thrombogenic gene mutations consisting of factor V G1691A, factor V H1299R (R2), factor II prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), MTHFR C677T, and MTHFR A1298C can identify individuals at risk for recurrent pregnancy loss.
Goodman
Cyle S
CS
Millenova Immunology Laboratories, 233 East Erie Street, Chicago, IL 60611, USA.
Coulam
Carolyn B
CB
Jeyendran
Rajasingam S
RS
Acosta
Vida A
VA
Roussev
Roumen
R
D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017354:Point Mutation; D011247:Pregnancy; D012307:Risk Factors; D019851:Thrombophilia / Q000235:genetics*