However , the relationship between haplotype and URPL must be further elucidated to obtain a more accurate assessment of the risk of URPL

However , the relationship between haplotype and URPL must be further elucidated to obtain a more accurate assessment of the risk of URPL. Additionally , serum homocysteine levels have been shown to be involved in URPL and are associated with the MTHFR 677C> T polymorphism. 9, 23, 24In general, the evidence shows that individuals with the MTHFR 677TT genotype have almost double the homocysteine levels as individuals carrying the E7820 MTHFR 677CT or 677CC genotypes. 9Therefore, we did not explore the relationship between serum homocysteine levels and URPL in this study. In summary, this study showed that individuals, specifically women of Chinese Han nationality in Hangzhou, who carry the MTHFR 677T allele and the 677T/1298A/2756A/66A/80G haplotype could be at an increased risk of URPL. 2 or more consecutive spontaneous abortions, which occur in 1% to 2% of women of childbearing age. 1, 2There are many causes of RPL, including chromosomal abnormalities, anatomic malformations, endocrine and metabolic imbalances, antiphospholipid antibody syndrome, hypothyroidism, autoimmune diseases, coagulant function abnormalities, exposure to poisons, reproductive tract infections, environmental factors, and so on. 3, 4Recurrent pregnancy loss with no clear cause is often called unexplained recurrent pregnancy loss (URPL). Regarding the etiologies of URPL, a number of studies have shown that a low level of folate and a high level of homocysteine in the folate metabolic pathway were significantly associated with URPL. 58The maintenance of normal levels of folate is dependent on food supply. Consumption of foods that lack folate, absorption disorders, and mutations in genes involved in metabolism could contribute to low levels of folate in some women. Some mutations in genes involved in the folate metabolic pathway have been associated with a low level of folate and a high level of homocysteine, such as polymorphisms of methylenetetrahydrofolate reductase (MTHFR), methionine synthase E7820 (MTR), methionine synthase reductase (MTRR), and reduced folate carrier 1 (RFC-1). Hence, it has been suggested that some genetic polymorphisms in genes of the folate metabolic pathway might impact the occurrence of URPL. Compared with the MTHFR 677CC genotype, carriers of the MTHFR 677TT genotype showed approximately 30% of enzyme activity, while carriers of the MTHFR 677CT genotype displayed almost 65% of normal enzyme activity. 9Reduced enzymatic activity could lead to dysfunction in the conversion of 510-methylenetetrahydrofolate to 5-methyltetrahydrofolate in vivo. Methionine synthase, which is a cobalamin (VB12)-dependent enzyme, combined with E7820 MTRR, which is required for the E7820 maintenance of MTR activity, plays an important role in the conversion of homocysteine into methionine. The RFC-1 is the primary carrier that transports 5-methyltetrahydrofolate into the cell, and an A80G mutation results in low levels of 5-methyltetrahydrofolate in cells. Dufficy et al showed that the amount of folate transported into cells was negatively correlated with the RFC-1 80G allele. 10Low levels of 5-methyltetrahydrofolate could inhibit the conversion of homocysteine into methionine, which in turn could cause elevated levels of homocysteine in vivo. Thrombophilia, vascular endothelial cell injury, and toxic effects on the embryo could result from a high level of homocysteine and could result in pregnancy loss. 1113At the same time, decreased levels of intracellular 5-methyltetrahydrofolate could result in low levels ofS-adenosylmethionine, a direct methyl donor, which could in turn affect the methylation processes of DNA, proteins, and lipids. However , many studies of gene variants in the folate metabolic pathway and URPL have mostly been concerned with the polymorphisms of MTHFR 677C> T and/or MTHFR 1298A> C; these studies have ignored the other relevant genes in the folate metabolic pathway. 5, 14, 15In addition, the association between the polymorphism of MTHFR 677C> T with URPL has remained controversial. 14, 15With regard to the different distributions of the polymorphisms of genes involved in folate metabolism in people from different regions, 5, 1416we performed a casecontrol study to ascertain the associations between polymorphisms in these genes with URPL in a Chinese Han population from the Hangzhou area. == Materials and Methods == == Participants == A total of 136 women who had 2 or more consecutive spontaneous abortions, E7820 including first, second, or third trimester losses, were recruited for this study from the outpatient Department of Obstetrics/Gynaecology and Genetics at Hangzhou First Peoples Hospital. Cryab All participants were enrolled prior to 12 weeks of gestation. The patients underwent standardized clinical and laboratory tests, which included evaluations of the following: parental karyotype analysis, hysteroscopy (prior to the current pregnancy), protein C, protein S, coagulation, sex hormones, thyroid function, human chorionic gonadotropin, genital tract secretions (eg, Ureaplasma urealyticum, Chlamydia trachomatis, andNeisseria gonorrhoeae), HIV antibodies, syphilis antibodies, TORCH, antinuclear antibodies, antineutrophil antibodies, and hepatitis B virus. In addition , semen examinations of the.