title: The significance of 1793G>A polymorphism in MTHFR gene in women with first trimester recurrent miscarriages.
abstract: BACKGROUND
  Recurrent miscarriages (RM) are significant social and clinical problem. One of suggested reason of RM is hyperhomocysteinemia. Polymorphic genes involved in homocysteine and folate metabolism, including 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, are considered as an important risk factors for homocysteine accumulation and modulator of RM susceptibility. Therefore the aim of this study was to evaluate the frequency of MTHFR polymorphisms (677C>T, 1298A>C, and 1793G>A) in women with recurrent miscarriages.
  
  
  METHODS
  We have analyzed 104 Polish women with a history of 3 or more unexplained recurrent miscarriages in the first pregnancy trimester (6-13 gestation week). The control group consisted of 169 women without obstetrical complication, any history of miscarriage and with at least one live birth in anamnesis. The investigated polymorphisms were determined by PCR/RFLP methods.
  
  
  RESULTS
  For MTHFR 1793G>A polymorphism we have observed significant overrepresentation of heterozygotic GA genotypes in RM group (15.38% vs. 4.14% in the controls, OR=4.21, p=0.003). For 677C>T and 1298A>C we have shown lack of significant association with RM. Nevertheless, such significant association was observed if more than one mutated MTHFR variant was present in one patient.
  
  
  CONCLUSIONS
  Our research indicate the possible role of MTHFR 1793G>A polymorphism in pathogenesis of RM. The noticed tendency to more frequent occurrence of haplotypes of MTHFR gene including two or three mutated alleles showed the possibility of summarized amplification of these variants effect influencing RM susceptibility.
authors.affiliation: Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Poznan, Poland. asm@data.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Seremak-Mrozikiewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Drews
authors.forename: Grazyna
authors.initials: G
authors.lastname: Kurzawinska
authors.forename: Anna
authors.initials: A
authors.lastname: Bogacz
authors.forename: Edmund
authors.initials: E
authors.lastname: Grzeskowiak
authors.forename: Przemyslaw M
authors.initials: PM
authors.lastname: Mrozikiewicz
mesh_terms: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2) / Q000235:genetics*; D000026:Abortion, Habitual / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D011044:Poland; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics
chemical_list: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2)