The factor V Leiden mutation may predispose women to severe preeclampsia

Preeclampsia and genetic risk factors for thrombosis: A case-control study

“…We found no differences m the prevalence of inherited nsk factors for venous thrombosis, mcluding factor V Leiden, prothrombm 20210A allele, and protem C, protem S, and antithrombin deficiencies, m women who had preeclampsia m their first pregnancy and in control subjects with an uneventful pregnancy This is in contrast with data from previous published studies 6 16,17 One explanation is the unexpectedly high frequency of factor V Leiden in the control group (9 2%) in this study We therefore compared the frequency of the factor V Leiden mutation among women who had preeclampsia with that of a different control group exammed previously 18 This group consisted of a subset of the original control group of the Leiden Thrombophilia Study In that study 474 consecutive patients with thrombosis were matched with 474 control subjects who either were acquamtances asked to participate by the patients or were partners of the patients From these control groups we selected, for the current analysis, women who had expenenced at least l pregnancy, had no history of venous thrombosis, were premenopausal, were not pregnant, were not in the puerperium, and had no recent miscarriäge (total women included, 105) 18 We found a higher frequency for factor V Leiden m women who had preeclampsia versus these control subjects (odds ratio, 3 70, 95% confidence interval, l 05 13 03) When we compare the frequency of the prothrombm 2021 OA allele among women who had preeclampsia with that of the same alternative control groupi 8 (total women included, 105, prothrombm 20210A allele positive, 3), no differences m frequency were found for prothrombm 20210A allele (odds ratio, l 08, 95% confidence interval, 0 25 4 60) DizonTownson et al 16 reported a frequency of factor V Leiden in an American obstetric populaüon of 4 2% (n = 403), which is similar to the frequency described m the Leiden Thrombophilia Study and a large Amencan study (3% 4%)''' and almost 3 times lower than the frequency obser\ed in the control subjects recruited m our studv Di/on-Townson et al l() also reported a frequency of factoi \ I eiden of 3% m an unselected group of gravid women Ho\\e\ei higher hequenciei o( factoi V Leiden have also Volume 181, Number 4 AmJ Obstet Gynecol DeGrootetal 979 been described by Pauer et al 21 ; frequencies of 9.2% (8/87 of an unselected group of healthy women with no history of fetal losses) and äs high äs 12% have been reported in some selected groups with a history of venous thrombosis or pulmonary embolism. 22 If the high frequency of factor V Leiden was too high in our control group, we can speculate about selection bias.…”

“…17 Differences in definition, methods, and cutoff levels used might explain the high frequency of activated protein C resistance. However, Dizon-Townson et al 16 described a frequency of factor V Leiden that was similar to that found in our study (n = 158, 8.9%) in women with severe preeclampsia. Recently, Kupfermine et al 6 reported a prevalence of 53% of inherited thrombophilia in women with severe preeclampsia, including 26% (9/34) with factor V Leiden.…”

“…Furthermore, it is unlikely that our results are explained by the geography of our population because the frequency of factor V Leiden was similar in the population of 2 different hospitals from 2 different regions of the country. Both groups had an identical ethnic origin (96% white), which was very similar to that described by Dizon-Townson et al 16 (94% white).…”

“…Bertina et al 7 have shown that 80% to 100% of persons with laboratory-confirmed activated protein C resistance are either heterozygous or homozygous for the factor V Leiden mutation. As suggested by Dizon-Townson et al, 16 the high rate of activated protein C resistance might be the result of a different definition of pregnancy-induced hypertension; 39% had chronic hypertension versus 3.1% in this study of women with preeclampsia, and 89% were nulliparous. 17 Differences in definition, methods, and cutoff levels used might explain the high frequency of activated protein C resistance.…”

Association analysis of nine missense polymorphisms in the coagulation factor V gene with severe preeclampsia in pregnant Japanese women

“…FV is activated by selective proteolytic cleavage that removes the large B domain, and FVa is inactivated by activated protein C (APC) (Rosing and Tans 1997). Association between preeclampsia and the Leiden mutation in F5 has been reported several times (Dizon-Townson et al 1996;Grandone et al 1997;Mimuro et al 1998;Nagy et al 1998b;Rigo et al 2000). The Leiden mutation is a single base mutation in the F5 gene that results in an amino acid substitution (R506Q) at a predominant APC-cleavage site and is a risk factor for familial venous thrombosis (Rosing and Tans 1997).…”