genetic polimorphisms of enzymes involved in folate metabolism in healthy slovenian population
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Abstract
Background. Enzymes that play a major role in folate metabolism are 5,10-methylenetetrahydrofolate reductase (MTHFR), thymidilate synthase (TS), methionine synthase (MS) and methionine synthase reductase (MTRR). Polymorphisms in their corresponding genes alter their enzymatic activity. The aim of this study was to determine the frequencies of polymorphic MTHFR and TS genotypes in healthy adults from Slovenian population in order to estimate the proportion of individuals that may be at risk for certain diseases or increased toxicity if treated with antifolate drugs.
Methods. MTHFR and TS polymorphisms were studied by a genotyping technique, based on polymerase chain reaction (PCR) followed by restriction enzyme analysis. DNA samples from 122 unrelated adult healthy subjects were obtained from the Tissue Typing Center and University Children’s Hospital in Ljubljana.
Results. In the analyzed group 62.3% of individuals carried at least one polymorphic MTHFR 677T allele and 52.5% carried at least one polymorphic 1298C allele. Only 12% of individuals had no polymorphic MTHFR allele. The frequencies of MTHFR genotypes were influenced by the age of the subjects under investigation. The frequency of the TS 3R/3R genotype in Slovenian population was significantly lower than in some other populations.
Conclusions. Genetic polymorphisms in folate metabolic pathway occur with high frequency in Slovenian population and modify cancer risk. Regarding the influence of these polymorphisms on the efficacy of treatment with antifolate drugs the introduced genotyping method could contribute to the individualization of treatment with methotrexate and 5-fluorouracil.
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bohanec2004zdravnikigenetic
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| Authors | ;Petra Bohanec;Vita Dolžan |
| Journal | planta medica |
| Year | 2004 |
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