Association of factor V gene polymorphisms (Leiden; Cambridge; Hong Kong and HR2 haplotype) with recurrent idiopathic pregnancy loss in Tunisia

Abstract

Inherited thrombophilia has been shown to be linked with fetal loss. We performed a case-control study on the association between thrombosis-related polymorphisms in the factor V (FV) gene (Leiden, Cambridge, Hong Kong; HR2 haplotype) and idiopathic recurrent pregnancy loss (RPL) in Tunisian women. A total of 348 women with RPL, and 203 control women were studied, corresponding to 1,250 pregnancy losses and 1,200 successful pregnancies. FV Leiden was seen in 19.4% of patients (4.3% in the homozygous state) and in 5.5% of controls. The prevalence of the FV HR2 haplotype was similar in patients and controls, but with 7 homozygous patients for 1 control. FV Cambridge and Hong Kong were absent from both patients and controls. The study of all pregnancy losses evidenced that the frequency of the factor V Leiden polymorphism was zero in women who had mis-carried before 7 weeks of gestation, and then sharply increased to a plateau. After categorization of pregnancy losses (before 8 weeks of gestation; weeks 8 and 9; weeks 10 to 12; from the 13th week of gestation onwards), heterozygous and homozygous factor V Leiden polymorphisms, and homozygous FV HR2 haplotype, were associated with significant and independent risks of pregnancy loss during weeks 8 and 9, which increased during weeks 10 to 12, then culminated after week 12. In Tunisian women with idiopathic RPL, factor V Leiden polymorphism and homozygous FV HR2 haplotype are not a risk factor for very early pregnancy loss, before 8 weeks of gestation, but are thereafter associated with significant clinical risks, which gradually increase from the 8th week onwards.

ORIGINAL ARTICLE: Lack of Consistent Association Between Endothelial Nitric Oxide Synthase Gene Polymorphisms, Homocysteine Levels and Recurrent Pregnancy Loss in Tunisian Women

“…As for diabetes, 23 coronary artery diseases 24 hypertension 25 and preeclampsia, 15 multiple genes encoding for proteins involved in numerous biological functions have been reported to be associated with RPL. Our previous studies and other data supported the role of thrombophilic genes, 26,27 cytokines genes 28,29 and of genes encoding biotransformation enzymes 12,30 in the physiopathology of RPL. However, a critical combination of variant necessary or sufficient to cause RPL has not yet been described.…”

Inherited thrombophilias and unexplained pregnancy loss: an incident case‐control study

“…Our study should avoid the heterogeneity of cases and controls studied in meta‐analyses which have until now supported this growing point of view. Incidentally, some authors suggest a threshold of 10 weeks of amenorrhea below which FVL would have no impact [32]. Moreover, among first degree relatives of vascular‐diseased probands, Coppens and co‐authors did not find any statistical differences in recurrence rates after a first pregnancy loss, between carriers and non‐carriers of the FVL or PTG mutations [33].…”

Thrombophilia investigation in Malaysian women with recurrent pregnancy loss

“…RPL has recently been defined by Farquharson 5 as three early (<12 weeks gestation) consecutive losses or two late (>12 weeks gestation) pregnancy losses. The three important thrombophilia markers are factor V Leiden mutation (FVL), 2,6,7 prothrombin G20210A mutation (PTG) 6,8 and activated protein C resistance (APC‐R) 9–12 …”