Author/Editor		Herman, Darja; Dolžan, Vita; Breskvar, Katja
Title		Genetic polymorphism of cytochromes P450 2C9 and 2C19 in Slovenian population
Translated title		Genetski polimorfizem citokromov P450 2C9 in 2C19 v slovenski populaciji
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 72, št. 6
Publication year		2003
Volume		str. 347-51
Language		eng
Abstract		Background. Cytochrome P4502C9 (CYP2C9) and 2CT 9 (CYP2C19) participate in metabolism of many clinically important drugs. Genetic polymorphisms of the CYP2C9 and CYP2C19 genes are described which may affect drug treatment The aim of this study was to determine the frequencies of polymorphic CYP2C9 and CYP2C19 alleles in Slovenian population in order to estimate the proportion of the population that might experience adverse drug reaction. Methods. The polymorphism of CYP2C9 and.CYP2C19 was analysed by a genotyping technique, based on polymerase chain reaction (PCR) followed by restriction enzyme analysis. DNA samples from 129 unrelated healthy subjects were obtained from the Blood Transfusion Centre of Slovenia and University Children š Hospital in Ljub jana. Results. In the analysed group of samples one-third of individuals carried at least one of the defective CYP2C9 alleles while among them 3.2% of individuals had both alleles affected. The frequencies of CYP2C9*2 and CYP2C9*3 were 0.122 and 0.063, respectively. Almost one-third of Slovenian individuals analysed carried at least one of the CYP2C19 polymorphic allele. The frequencies of CYP2C19*2 and CYP2C19*3 were 0.159 and 0.004, respectively. Conclusions. The results of our study indicate that approximately one-third of the patients from Slovenian population may require either adjustments of dose or increased monitoring when initiating treatment with CYP2C9 and CYP2C19 substrates having a narrow therapeutic index. High risk of adverse drug reaction may be expected in 1-3% of eventual patients.
Summary		Izhodišča. Citokromi P4502C9 (CYP2C9) in 2C19 (CYP2C19) so vključeni v presnovo različnih zdravil. Kodirata jih polimorfna gena CYP2C9 in CYP2C79, zaradi česar prihaja do interindividualnih razlik v hitrosti in učinkovitosti zdravljenja. Genetski polimorfizem postane klinično pomemben predvsem pri zdravilih, ki imajo majhno terapevtsko širino. Namen raziskave je bil določiti frekvence polimorfnih alelov CYP2C9 in CYP2C19 v slovenski populaciji in na ta način oceniti delež posameznikov s povečanim tveganjem za nastanek neželenih učinkov zdravila. Metode. Polimorfizem genov CYP2C9 in CYP2C19 smo analizirali s tehniko genotipizacije. Ta temelji na pomnoževanju ustreznega dela genomske DNK z verižno reakcijo s polimerazo in na cepitvi pomnoženega odseka z ustreznim encimom. Uporabili smo vzorce DNK 129 nesorodnih, zdravih posameznikov ki smo jih dobili na Centru za transfuzijo Republike Slovenije in na Pediatrični kliniki v Ljub jani. Rezultati. Vanalizirani skupini smo zasledili, da je ena tretjina posameznikov imela vsaj enega od polimorfnih alelov CYP2C9 med njimi pa je bilo 3,2% posameznikov z obema polimorfnima aleloma. Frekvenci alelov CYP2C9'*2 in CYP2C9*3 sta bili 0,122 oz 0, 063. Podobno je skoraj ena tretjina posameznikov imela vsaj enega od polimorfnih alelov CYP2C19. Frekvenci alelov CYP2C19*2 in CYP2C19'*3 sta bili 0,159 oz 0,004. Zaključki. Rezultati naše raziskave kažejo, da ima približno tretjina Slovencev zmanjšano metabolno kapaciteto za zdravila ki se presnavljajo prek CYP2C9 oz. CYP2C19. Takim osebam bi bilo treba medzdravljenjem zzdravili z majhno terapevtsko širino ustrezno prilagoditi odmerek zdravila oz natančneje spremljati potek zdravljenja, še posebno v obdobju uvajanja zdravila. Pri 1-3 % takšnih posameznikov pa je večja verjetnost pojava hujših neželenih učinkov zdravil
Descriptors		POLYMORPHISM (GENETICS) CYTOCHROME P-450 ALLELES GENOTYPE POLYMERASE CHAIN REACTION SLOVENIA