Inherited thrombophilia in recurrent spontaneous abortion among Chinese women

Approximately 1% to 2% of women of reproductive age will experience recurrent spontaneous abortions (RSAs). However, after chromosomal, endocrine, infectious, anatomic, and autoimmune causes have been ruled out, more than 50% of patients with RSA remain unexplained [1]. Pregnancy is an acquired hypercoagulable state with an increased thrombotic risk, and genetic factors have been identified as being associated with an increased risk of venous thrombosis. This study was conducted to determine genetic factors associated with RSA among Chinese women (these factors are listed in the Table 1). Between January 1999 and September 2002, 148 women with unexplained RSAs were selected at the Department of Obstetrics and Gynecology of Renji Hospital, Shanghai Second Medical University, Shanghai, China, and matched with 82 healthy pregnant women. The diagnosis of “unexplained” RSA was made according to practice guidelines followed at this hospital [2]. On laboratory tests the women did not have acquired thrombophilia factors such as antiphospholipid or lupus anticoagulant. Genomic DNA was extracted from peripheral blood leucocytes by the hydroxybenzene–chloroform method. The polymerase chain reaction–restriction fragment length polymorphism method (PCR-RFLP) was used to detect factor V Leiden G1691A and prothrombin G20210A, as well as 677C → T and 1298A → C polymorphisms of the 5,10–methylenetetrahydrofolate reductase (MTHFR) gene. Amplified DNA fragments were cut with restriction enzymes Mnl I, Hind III, Hinf I, and Mbo II (New England Biolabs, Boston, Mass, USA), and the digested PCR products were separated by electrophoresis in 12% polyacrylamide gel and detected by the silver staining method. The distribution of thrombophilia gene polymorphism was analyzed by the χ2 and Fisher exact tests using SPSS statistical software, version 11.01 (SPSS, Chicago, Ill, USA); P < .05 was considered significant. Two gene polymorphisms associated with increased risk of venous thromboembolism, factor V Leiden G1691A and prothrombin G20210A, were identified neither in the women who had RSAs nor in the healthy controls. A previous study demonstrated that those gene defects seemed to occur more frequently in the caucasoid population and had different loci in the Chinese population [3]. However, 2 loci in the MTHFR gene showed polymorphism in this study (677C → T and 1298A → C). The thrombophia allele 677T conferred the susceptibility to RSA (Table 1), whereas 677CC was found significantly less frequently in women with RSAs. There was no close association between MTHFR polymorphism 1298A → C and RSA. When analyzing the linkage of both polymorphisms, the linkage phenotype 677C → T + 677TT/1298CC increased RSA frequency and the protective phenotype 677CC/1298AA decreased RSA frequency among women with a history of RSA compared with controls, with statistical significance (Table 1). This study suggested that MTHFR might be the key thrombophilia gene conferring susceptibility to RSA in Chinese women. Because of the role of MTHFR in the metabolism of homocysteine, it may be advisable to measure the plasma level of total homocysteine and prescribe folic acid supplement to women who have a history of RSA [4]. This work was supported Grant 01QB14023 from Shanghai's Scientific Star.