| 1. |
- Altmae, Signe, et al.
(författare)
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Variations in folate pathway genes are associated with unexplained female infertility
- 2010
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 94:1, s. 130-137
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate associations between folate-metabolizing gene variations, folate status, and unexplained female infertility. Design: An association study. Setting: Hospital-based IVF unit and university-affiliated reproductive research laboratories. Patient(s): Seventy-one female patients with unexplained infertility. Intervention(s): Blood samples for polymorphism genotyping and homocysteine, vitamin B12, and folate measurements. Main Outcome Measure(s): Allele and genotype frequencies of the following polymorphisms: 5,10-methylenetetra-hydrofolate reductase (MTHFR) 677C/T, 1298A/C, and 1793G/A, folate receptor 1 (FOLR1) 1314G/A, 1816delC, 1841G/A, and 1928C/T, transcobalamin II (TCN2) 776C/G, cystathionase (CTH) 1208G/T and solute carrier family 19, member 1 (SLC19A1) 80G/A, and concentrations of plasma homocysteine, vitamin B12, and serum folate. Result(s): MTHFR genotypes 677CT and 1793GA, as well as 1793 allele A were significantly more frequent among controls than in patients. The common MTHFR wild-type haplotype (677, 1298, 1793) CAG was less prevalent, whereas the rare haplotype CCA was more frequent in the general population than among infertility patients. The frequency of SLC19A1 80G/A genotypes differed significantly between controls and patients and the A allele was more common in the general population than in infertile women. Plasma homocysteine concentrations were influenced by CTH 1208G/T polymorphism among infertile women. Conclusion(s): Polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. (Fertil Steril (R) 2010;94:130-7. (C) 2010 by American Society for Reproductive Medicine.)
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| 2. |
- Lokk, Kaie, et al.
(författare)
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DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns
- 2014
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Ingår i: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X. ; 15:4, s. r54-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: DNA epigenetic modifications, such as methylation, are important regulators of tissue differentiation, contributing to processes of both development and cancer. Profiling the tissue-specific DNA methylome patterns will provide novel insights into normal and pathogenic mechanisms, as well as help in future epigenetic therapies. In this study, 17 somatic tissues from four autopsied humans were subjected to functional genome analysis using the Illumina Infinium HumanMethylation450 BeadChip, covering 486 428 CpG sites. RESULTS: Only 2% of the CpGs analyzed are hypermethylated in all 17 tissue specimens; these permanently methylated CpG sites are located predominantly in gene-body regions. In contrast, 15% of the CpGs are hypomethylated in all specimens and are primarily located in regions proximal to transcription start sites. A vast number of tissue-specific differentially methylated regions are identified and considered likely mediators of tissue-specific gene regulatory mechanisms since the hypomethylated regions are closely related to known functions of the corresponding tissue. Finally, a clear inverse correlation is observed between promoter methylation within CpG islands and gene expression data obtained from publicly available databases. CONCLUSIONS: This genome-wide methylation profiling study identified tissue-specific differentially methylated regions in 17 human somatic tissues. Many of the genes corresponding to these differentially methylated regions contribute to tissue-specific functions. Future studies may use these data as a reference to identify markers of perturbed differentiation and disease-related pathogenic mechanisms.
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| 3. |
- Murto, Tiina, 1975-, et al.
(författare)
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Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR) gene variations in relation to IVF pregnancy outcome
- 2014
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:1, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study folic acid intake, folate status and pregnancy outcome after infertility treatment in women with different infertility diagnoses in relation to methylenetetrahydrofolate reductase (MTHFR) 677C>T, 1298A>C and 1793G>A polymorphisms. Also the use of folic acid supplements, folate status and the frequency of different gene variations were studied in women undergoing infertility treatment and fertile women.DESIGN: Observational study.SETTING: University hospital.POPULATION: Women undergoing infertility treatment and healthy, fertile, non-pregnant women.METHODS: A questionnaire was used to assess general background data and use of dietary supplements. Blood samples were taken to determine plasma folate and homocysteine levels, and for genomic DNA extraction. A comparison of four studies was performed to assess pregnancy outcome in relation to MTHFR 677 TT vs. CC, and 1298 CC vs. AA polymorphisms.MAIN OUTCOME MEASURES: Folic acid supplement intake, and plasma folate, homocysteine and genomic assays.RESULTS: Women in the infertility group used significantly more folic acid supplements and had better folate status than fertile women, but pregnancy outcome after fertility treatment was not dependent on folic acid intake, folate status or MTHFR gene variations.CONCLUSION: High folic acid intakes and MTHFR gene variations seem not associated with helping women to achieve pregnancy during or after fertility treatment.
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| 4. |
- Nilsson, Torbjörn K., 1956-, et al.
(författare)
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A folate receptor alpha double-mutated haplotype 1816delC-1841A is distributed throughout Eurasia and associated with lower erythrocyte folate levels
- 2012
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Ingår i: Molecular Biology Reports. - Dordrecht, Netherlands : Springer. - 0301-4851 .- 1573-4978. ; 39:4, s. 4471-4478
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Tidskriftsartikel (refereegranskat)abstract
- Folate is crucial for various cellular functions. Several transport mechanisms allow folate to enter the intracellular compartment with folate receptor-alpha being the major high-affinity receptor. Rare genetic variations in exons of the FR-alpha gene, FOLR1, were recently shown to cause severe folate deficiency accompanied by neurological and other disturbances. So far, similar effects by genetic variation in noncoding parts of the FOLR1 gene have not been identified. The aim of our study was to determine biochemically the haplotype structure of two linked polymorphisms in the FOLR1 gene, 1816delC and 1841G > A, the prevalences of the mutated alleles across Eurasia, and their possible effects on physiological folate levels in vivo. For this purpose we employed allele-specific PCR and Pyrosequencing technology and performed genotyping in 738 subjects from Spain, 387 from Sweden, 952 from Estonia, and 47 from Korea. We demonstrate the presence of an ancient double-mutated haplotype 1816delC-1841A in the FOLR1 gene, with the prevalence of the mutated allele being highest among Koreans (q = 0.074), lower in Estonians (q = 0.017), Spaniards (q = 0.0061), and the lowest among Swedes (q = 0.0026). Erythrocyte folate levels were studied in the Spanish population sample, where subjects carrying the double-mutated FOLR1 haplotype had significantly reduced levels by 27% (P = 0.039), adjusted for serum vitamin B-12 levels and MTHFR 677C > T genotype, while the mean serum folate levels were only 20% lower among the carriers (P = 0.11). Plasma homocysteine and cobalamin levels did not differ. Thus, we have demonstrated by molecular haplotyping an ancient double-mutated haplotype 1816delC-1841A in the FOLR1 gene, spread over the whole Eurasian continent, which may be of functional importance for uptake of folate in red blood cells.
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