title: Association between MTHFR 1298A>C polymorphism and spontaneous abortion with fetal chromosomal aneuploidy.
abstract: PROBLEM  Polymorphisms in genes involved in folate metabolism are commonly associated with defects in folate-dependent homocysteine metabolism, which can result in DNA hypomethylation and chromosome nondisjunction. This prospective study aimed to investigate the associations between MTHFR 677C>T, MTHFR 1298A>C, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68 polymorphisms and spontaneous abortion (SA) with fetal chromosomal aneuploidy. METHOD OF STUDY  Subjects included 33 SA with normal fetal karyotype, 24 SA with fetal chromosomal aneuploidy and 155 normal controls. Polymorphisms were genotyped by PCR-RFLP and QF-PCR analysis. RESULTS  The frequencies of MTHFR 1298AC and combined 1298AC/CC genotypes were higher in SA with fetal chromosomal aneuploidy than in controls. The 1298C allele frequency was also significantly higher in SA with fetal chromosomal aneuploidy than in controls. Moreover, the 1298C allele frequency was higher in SA with fetal chromosomal aneuploidy than in SA with normal fetal karyotype. The combined 1298AC/CC genotype was significantly associated with the risk of SA with fetal chromosomal aneuploidy compared with that of the 1298AA genotype (adjusted OR = 2.93, 95% CI: 1.11-7.69). There was no association between SA with fetal chromosomal aneuploidy and other polymorphisms. CONCLUSIONS  Our findings indicate that MTHFR 1298A>C polymorphism may be an independent risk factor for SA with fetal chromosomal aneuploidy.
authors.affiliation: Laboratory of Medical Genetics, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Kim
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Choi
authors.forename: Do Jin
authors.initials: DJ
authors.lastname: Kim
authors.forename: Shin Yeong
authors.initials: SY
authors.lastname: Lee
authors.forename: Ji Hyae
authors.initials: JH
authors.lastname: Lim
authors.forename: Jung Yeol
authors.initials: JY
authors.lastname: Han
authors.forename: Hyun Mee
authors.initials: HM
authors.lastname: Ryu
authors.forename: Min Hyoung
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000782:Aneuploidy; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D005333:Fetus; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D059785:Karyotype; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011446:Prospective Studies; D056910:Republic of Korea; D012307:Risk Factors
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)