15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Almost 1600 individuals from the Polish population were recruited to this study. Among them 319 were fertile couples, 289 were recurrent spontaneous abortion (RSA) couples, and 131 were in the group of recurrent implantation failure (RIF) following in vitro fertilization. The aim of this study was to evaluate the MTHFR c.c.677 C>T and c.c.1298 A>C polymorphisms’ association with RSA and RIF. We used PCR-RFLP with HinfI (677 C>T) and MboII (1298 A>C) digestion. We observed a protective effect of the female AC genotype (OR = 0.64, p = 0.01) and the C allele (AC+CC genotypes; OR = 0.65, p = 0.009) against RSA. Moreover, 1298 AA/677 CT women were more frequent in RSA (31.14%) and RIF (25.20%) groups in comparison to fertile women (22.88%), although this difference was significant only in the case of RSA ( p = 0.022, OR = 1.52). Male combined genotype analysis revealed no association with reproductive failure of their partners. Nevertheless, the female/male combination AA/AC of the 1298 polymorphism was more frequent in RSA couples ( p = 0.049, OR = 1.49). However, the significant results became insignificant after Bonferroni correction. In addition, analysis of haplotypes showed significantly higher frequency of the C/C haplotype (1298 C/677 C) in the female control group than in the female RSA group ( p = 0.03, OR = 0.77). Moreover, the association between elevated homocysteine (Hcy) level in plasma of RSA and RIF women and MTHFR polymorphisms was investigated but did not reveal significant differences. In conclusion, for clinical practice, it is better to check the homocysteine level in plasma and, if the Hcy level is increased, to recommend patients to take folic acid supplements rather than undergo screening of MTHFR for 1298 A>C and 677 C>T polymorphisms.

          Related collections

          Most cited references31

          • Record: found
          • Abstract: found
          • Article: not found

          A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity.

          A common mutation in methylenetetrahydrofolate reductase (MTHFR), C677T, results in a thermolabile variant with reduced activity. Homozygous mutant individuals (approximately 10% of North Americans) are predisposed to mild hyperhomocysteinemia, when their folate status is low. This genetic-nutrient interactive effect is believed to increase the risk for neural tube defects and vascular disease. In this communication, we characterize a second common variant in MTHFR (A1298C), an E to A substitution. Homozygosity was observed in approximately 10% of Canadian individuals. This polymorphism was associated with decreased enzyme activity; homozygotes had approximately 60% of control activity in lymphocytes. Heterozygotes for both the C677T and the A1298C mutation, approximately 15% of individuals, had 50-60% of control activity, a value that was lower than that seen in single heterozygotes for the C677T variant. No individuals were homozygous for both mutations. Additional studies of the A1298C mutation, in the absence and presence of the C677T mutation, are warranted, to adequately address the role of this new genetic variant in complex traits. A silent genetic variant, T1317C, was identified in the same exon. It was relatively infrequent (allele frequency 5%) in our study group, but was quite common in a small sample of African individuals (allele frequency 39%). Copyright 1998 Academic Press.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The 1298A-->C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine.

            I Weisberg (2001)
            A common mutation in methylenetetrahydrofolate reductase (MTHFR), 677C-->T, is associated with reduced enzyme activity, a thermolabile enzyme and mild hyperhomocysteinemia, a risk factor for vascular disease. Recently, a second common mutation (1298A-->C; glutamate to alanine) was reported, but this mutation was suggested to increase homocysteine only in individuals who carried the bp677 variant. To evaluate the functional consequences of this mutation, we performed site-directed mutagenesis and in vitro expression. For in vivo assessment of clinical impact, we examined the 1298A-->C genotypes and plasma homocysteine in 198 individuals from the NHLBI Family Heart Study that had previously been assessed for the 677 substitution. Site-directed mutagenesis of the human cDNA was performed to generate enzymes containing each of the two mutations, as well as an enzyme containing both substitutions. Enzyme activity and thermolability were assessed in bacterial extracts. The activity of the wild-type cDNA was designated as 100%; mutant enzymes containing the 1298 and 677 mutations separately had 68% (+/-5.0) and 45% (+/-10.8), respectively, of control activity while the enzyme containing both mutations had 41% (+/-12.8) of control activity. The 1298 mutation was not associated with a thermolabile enzyme. In the Family Heart Study, fasting homocysteine was significantly higher (P T variant. This study suggests that two variants in MTHFR should be assessed as genetic risk factors for hyperhomocysteinemia.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Systematic review and meta-analysis of genetic association studies in idiopathic recurrent spontaneous abortion.

              1) To perform the first comprehensive systematic review of genetic association studies (GASs) in idiopathic recurrent spontaneous abortion (IRSA); 2) to analyze studies according to recurrent spontaneous abortion (RSA) definition and selection criteria for patients and control subjects; and 3) to perform meta-analyses for the association of candidate genes with IRSA.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Visualization
                Role: Formal analysisRole: InvestigationRole: Visualization
                Role: Formal analysisRole: Software
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: InvestigationRole: Resources
                Role: Formal analysisRole: Software
                Role: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 October 2017
                2017
                : 12
                : 10
                : e0186022
                Affiliations
                [1 ] Department of Clinical Immunology, Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
                [2 ] Department of Surgical, Endoscopic and Oncologic Gynecology, Polish Mothers’ Memorial Hospital–Research Institute, Łódź, Poland
                [3 ] Department of Gynecology and Gynecologic Oncology, Polish Mothers’ Memorial Hospital–Research Institute, Łódź, Poland
                [4 ] Department of Reproductive Medicine, Gameta Hospital, Rzgów, Poland
                [5 ] Biogeno–Regional Science-Technology Center, Podzamcze, Poland
                [6 ] First Chair and Clinic of Obstetrics and Gynecology, Medical University of Warsaw, Warszawa, Poland
                [7 ] Department of Medical Genetics, Center of Biostructure Research, Medical University of Warsaw, Warszawa, Poland
                [8 ] Faculty of Physical Education and Physiotherapy, Opole University of Technology, Opole, Poland
                [9 ] Obstetric Gynecological Department, District Hospital Strzelce Opolskie, Strzelce Opolskie, Poland
                [10 ] APC–Medical Analyses, Łódź, Poland
                [11 ] Department of Genomics, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland
                Universite Clermont Auvergne, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist. APC – Medical Analyses does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-9127-1089
                Article
                PONE-D-17-17489
                10.1371/journal.pone.0186022
                5657620
                29073227
                e63459ce-5399-473f-b9c2-e10ef447a554
                © 2017 Nowak et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 May 2017
                : 22 September 2017
                Page count
                Figures: 0, Tables: 3, Pages: 11
                Funding
                Funded by: National Science Centre, Poland
                Award ID: 2014/13/B/NZ5/00273 and N N401 588340
                Award Recipient :
                This work was supported by National Science Centre, Poland, 2014/13/B/NZ5/00273 and N N401 588340, Dr. Izabela Nowak and Wroclaw Centre of Biotechnology, the programme The Leading National Research Centre (KNOW) for years 2014–2018 (to I. Nowak, Ph.D.).
                Categories
                Research Article
                Biology and Life Sciences
                Genetics
                Heredity
                Genetic Mapping
                Variant Genotypes
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Pregnancy Complications
                Miscarriage
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Pregnancy Complications
                Miscarriage
                Biology and Life Sciences
                Genetics
                Heredity
                Genetic Mapping
                Haplotypes
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Biology and Life Sciences
                Developmental Biology
                Embryology
                Embryos
                Biology and Life Sciences
                Genetics
                Mutation
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Vitamins
                B Vitamins
                Folic Acid
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Vitamins
                B Vitamins
                Folic Acid
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article