title: Polymorphisms of Genes Involved in the Folate Metabolic Pathway Impact the Occurrence of Unexplained Recurrent Pregnancy Loss.
abstract: Low levels of folate combined with high levels of homocysteine may cause unexplained recurrent pregnancy loss (URPL). However, the relationships between polymorphisms in genes of the folate metabolic pathway and URPL remain controversial. We conducted a case-control study to explore polymorphisms of the major folate pathway genes, including methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, methionine synthase (MTR) 2756A>G, methionine synthase reductase (MTRR) 66A>G and reduced folate carrier 1 (RFC-1) 80A>G, and their associations with URPL. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the distributions of MTHFR, MTR and RFC-1 polymorphisms, and the results were validated using direct sequencing. The polymorphisms in MTRR were determined using direct sequencing. Haplotypes were analyzed using SHEsis, an online tool for biological analysis. We found that the MTHFR 677T allele and the 677T/1298A/2756A/66A/80G haplotype were risk factors for URPL, while the MTR 2756G allele and the 677C/1298A/2756A/66A/80A haplotype exhibited protective effects on susceptibility to URPL in a Chinese Han population from the Hangzhou area.
authors.affiliation: School of Laboratory Medicine & Life Science, Wenzhou Medical University, Wenzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Guangchao
authors.initials: G
authors.lastname: Zhuo
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Chunning
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Qiaofeng
authors.initials: Q
authors.lastname: Tu
authors.affiliation: Department of Obstetrics/Gynaecology and Genetics, Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Obstetrics/Gynaecology and Genetics, Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics/Gynaecology and Genetics, Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Qian
authors.affiliation: School of Laboratory Medicine & Life Science, Wenzhou Medical University, Wenzhou, China Department of Laboratory Medicine, Hangzhou First People's Hospital, Hangzhou, China wangxj0525@126.com.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Wang
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000026:Abortion, Habitual / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human
keywords: folate metabolism; gene polymorphism; haplotype; unexplained recurrent pregnancy loss