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

Abstract

The Leiden mutation in the coagulation factor V (F5) gene associated with preeclampsia in Caucasians has not been found in Japanese populations. We examined the association of 20 missense polymorphisms in the F5 gene in 133 pregnant Japanese women with preeclampsia and in 224 unrelated, healthy, pregnant Japanese women. Among nine polymorphisms identified in the subjects, the M385T and R485K polymorphisms were associated with preeclampsia (P ϭ 0.05 and P ϭ 0.02, respectively). Haplotype analysis indicated that the R485K polymorphism is truly associated with preeclampsia, whereas the association of the M385T polymorphism is due to linkage disequilibrium. Taken together with reports that the R485 allele yields poor factor V function in comparison with that of the K485 allele and that the F5 Leiden mutation is associated with preeclampsia in Caucasian populations, the findings of the present study suggest that the F5 gene is associated with preeclampsia in pregnant Japanese women.

MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: a case control study

“…A previous study investigated the role of 20 missense variations of the F5 gene in Japanese preeclamptic women, including F5:c.6665A > G and indicated the significant association of only two variants rs6033 and rs6020. F5:c.6665A > G variant was not found significant in association with preeclampsia in Japanese patients [10], which is in disagreement with our findings revealing decrease risk to preeclampsia. F5:c.6665A > G results in the substitution of aspartic acid into glycine in the C2 terminal domain of the F5 gene.…”

“…The substitution may affect the hydrogen bond formation, ionic interaction and rigidity of the protein. It may have an influence on the conformational changes in the protein and may be associated with unexplained activated protein C (APC) resistance [9][10][11]. F5:c.6665A > G has been reported as the likely benign functional variant and have significantly higher frequency among Asians and Arabians [30].…”

“…The products of these genes play a crucial role in the mechanism required for the normal development and functioning of the placenta [7,8]. The functional genetic variations in the genes affect the thrombogenic and angiogenic properties which lead to abnormalities of the placenta and result in preeclampsia [9][10][11]. The common SNVs found in association with preeclampsia include F5: c.1601G > A (rs6025), MTHFR: c.665C > T (rs1801133), MTHFR: c.1286A > C (rs1801131), VEGFA: c.-2055A > C (rs699947) and VEGFA: c.*237C > T (rs3025039) [12][13][14].…”

Prevalence of factor V Leiden and prothrombin G20210A mutations in Chinese patients with deep venous thrombosis and pulmonary embolism

“…Until now, except generally accepted acquired risk factors for VTE, genetic risk factors responsible for thrombophilia have also been recognized to have an important role in Caucasian populations. Human factor V circulates in the plasma as a 330-kDa single chain glycoprotein (Watanabe et al, 2002); the factor V Leiden mutation is the most common genetic risk factor for VTE among Caucasians, with a prevalence of between 2% and 15% in the general population (Rees, Cox & Clegg, 1995). This amino acid substitution slows down the inactivation of factor V a by activated protein C (APC), thus resulting in impaired control of the coagulation cascade.…”

Inherited defects of coagulation Factor V: the thrombotic side

“…The R455K polymorphism is not very well characterized, although it has frequently been associated with risk of arterial or venous disease in Oriental populations, in which the 455Lys‐allele is the most common allele. In these populations, the 455Lys‐alelle has been associated with venous thrombosis [17], with heart disease and a reduced normalized APC sensitivity [18] and with pre‐eclampsia [19]. The latter disease association was also reported in a Finnish population [20].…”