Author/Editor		Smerkolj, Sava; Popović, Mara; Glavač, Damjan
Title		Iskanje genetskih sprememb ter polimorfizem kodona 129 gena PRNP v zdravi slovenski populaciji in sporadičnih primerih Creutzfeldt-Jakobove bolezni
Translated title		Screening for genetic changes and codon 129 polymorphism in PRNP gene in healthy Slovenian population and sporadic cases of Creutzfeldt-Jakob disease
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 73, št. 11
Publication year		2004
Volume		str. 803-6
Language		slo
Abstract		Background. Prion protein has an important role in development of prion diseases, fatal neurodegenerative disorders. As the codon 129 genotype of the prion protein gene (PRNP) is a known susceptibility factor for the diseases, we wanted to determine its distribution in healthy Slovenian population and also in cases of sporadic Creutzfeldt-Jakob disease (sCJD). Furthermore, we wanted to screen the whole gene in order to establish the presence of genetic changes. Methods. We screened 350 DNA samples of healthy blood donors and 12 DNA samples of patients deceased of sCJD. After the amplification and conformation analysis had been done, the gene was sequenced using an automatic sequencer Results. Methionine homozygotes comprised 46 8% of healthy population, valine homozygotes 12.1% and heterozygotes 41.1%; out of 12 sCJD patients 10 were methionine homozygotes (83.3%), 1 was valine homozygote (8.3%) aud 1 was heterozygote (8.3%). Found SNPs were combination of codon 76 change (228C > T) and codon 84 change (252T > C) in a single sample of healthy population, combination of codon 68 change (204T > C) and codon 76 change (228C > T) in two samples of healthy population and codon 117 change (351A > G) in a healthy population sample and in a valine homozygote patient. Conclusions. In comparison to the pooled Caucasian population is genotype M/M frequency slightly increased on account of decreased genotype M/V frequency in healthy Slovenian population, suggesting a little higher risk for acquiring a new variant of CJD (vCJD), because up to date all confirmed vCJD cases except one heterozygote were methionine homozygotes. Codon 129 genotype distribution in sCJD can be described as disease-specific. The absence of pathogenic mutations in sCJD patients confirms the non familial, sporadic disease form.
Summary		Izhodišča. Prionski protein ima pomembno vlogo pri nastanku prionskih bolezni, usodnih nevrodegenerativnih obolenj. Genotip kodona 129 gena za prionski protein (PRNP) je znan dovzetnostni dejavnik za te bolezni, zato smo želeli določiti njegovo razporeditev v zdravi slovenski populaciji in pri sporadičnih primerih Creutzfeldt-Jakobove bolezni (sCJB). Poleg tega smo želeli pregledati celoten PRNP, da bi ugotovili prisotnost genetskih sprememb. Metode. Pregledali smo 350 vzorcev DNK zdravih krvodajalcev in 12 vzorcev DNK bolnikov, umrlih za sCJB. Gen smo pomnožili z verižno reakcijo s polimerazo in mu po konformacijski analizi z avtomatskim sekvenatorjem določili zaporedje. Rezultati. V zdravi populaciji je bilo 46,8% metioninskih homozigotov, 12,1% valinskih homozigotov, 41,1% heterozigotov. Od 12 bolnikov s sCJB pa je bilo 10 metioninskih homozigotov (83,3%), 1 valinski homozigot (8,3%) in 1 heterozigot (8,3%). Tako v zdravi populaciji kot pri enem bolniku smo našli tihe spremembe enega nukleotida: kombinacija spremembe na kodonu 76 (228C > T) in kodonu 84 (252T > C) pri enem vzorcu zdrave populacije, kombinacija spremembe na kodonu 68 (204T > C) in kodonu 76 (228C > T) pri dveh vzorcih zdrave populacije ter sprememba na kodonu 117 (351A > G) pri enem vzorcu zdrave populacije in pri enem bolniku. Zaključki. V primerjavi s povprečjem evropske populacije rahlo povečana frekvenca genotipa M/M na račun zmanjšane frekvence genotipa M/V v zdravi slovenski populaciji kaže na nekoliko povečano tveganje za novo različico CJB (v CJB), pri kateri so vsi doslej ugotovljeni primeri, razen enega heterozigota, metioninski homozigoti. Razporeditev pri bolnikih kaže na razporeditev, specifično za sCJB. Na podlagi odsotnosti patogenih mutacij smo potrdili, da gre pri bolnikih za nedružinsko, sporadično obliko bolezni.
Descriptors		CREUTZFELDT-JAKOB SYNDROME POLYMORPHISM (GENETICS) PRIONS GENOTYPE POLYMERASE CHAIN REACTION BASE SEQUENCE POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL