Author/Editor     Bohanec, Petra; Dolžan, Vita
Title     Genetski polimorfizmi encimov v presnovni poti folata v zdravi slovenski populaciji
Translated title     Genetic polimorphisms of enzymes involved in folate metabolism in healthy Slovenian population
Type     članek
Source     Zdrav Vestn
Vol. and No.     Letnik 73, št. 11
Publication year     2004
Volume     str. 807-13
Language     slo
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.
Summary     Izhodišča. V presnovni poti folata imajo pomembno vlogo encimi 5,10-metilentetrahidrofolatreduktaza (MTHFR), timidilat sintaza (TS), metionin sintaza (MS) in metionin sintaze reduktaza (MTRR). Polimorfizmi v pripadajočih genih spremenijo encimsko aktivnost. Namen raziskave je bil določiti pogostnost polimorfnih genotipov MTHFR in TS v slovenski populaciji in s tem oceniti, kolikšen delež posameznikov bi lahko bil bolj izpostav len nekaterim boleznim in toksičnim učinkom antagonistov folata. Metode. Polimorfizme genov v presnovni poti folata smo določali z metodo genotipizacije, ki temelji na pomnoževanju dela genomske DNK z verižno reakcijo s polimerazo in cepitvi pomnoženega odseka z ustreznim encimom. Za analizo smo uporabili vzorce DNK 122 nesorodnih zdravih odraslih oseb, ki smo jih dobili na Centru za tipizacijo tkiv in na Pediatričnikliniki v Ljubljani. Rezultati. Kar 62,3% preiskovancev je imelo vsaj en polimorfen alel MTHFR G77T, 52,5% pa vsaj en polimorfen alel 1298 C. Le 12% preiskovancev ni imelo nobenega od analiziranih polimorfizmov v genu za MTHFR. Primerjava naših rezultatov z izsledki drugih študij je pokazala, da na, frekvence polimorfnih genotipov MTHFR vpliva starost preiskovancev. Frekvenca genotipa TS3R/3R je bila v našem vzorcu nižja kot pri drugih populacijah. Zaključki. Polimorfizmi v presnovni poti folata so v slovenski populaciji pogosti in vplivajo na tveganje za nekatere oblike raka. Ker ti polimorfizmi lahko vplivajo tudi na uspešnost zdravljenja z antagonisti folata, bi lahko z opisanimi metodami genotipizacije prispevali k individualizaciji zdravljenja z metotreksatom in 5-fluorouracilom.
Descriptors     FOLIC ACID
POLYMORPHISM (GENETICS)
METHYLENETETRAHYDROFOLATE DEHYDROGENASE
GENOTYPE
METHIONYL T RNA SYNTHETASE
TETRAHYDROPTEROYLGLUTAMATE METHYLTRANSFERASE
POLY DA-DT
POLYMERASE CHAIN REACTION
POLYMORPHISM, RESTRICTION FRAGMENT LENGTH