PRNP promoter region polymorphism in Creutzfeldt-Jakob disease
Pawel P. Liberski^, Jolanta Bratosiewicz-W^sik J^, Anna Zielinska^, Gerard H. Jansen^ and Tomasz J. W^sik^
^Dept. Mol. Pathol. Neuropathol., Med. Univ. Lodz, Czechoslowacha street 8/10; PL 92-216 Lodz, Poland ^Dept. Virology, University of Sile- sia in Katowice, Poland ^Department of Laboratory, Medicine Ottawa, Ontario, Canada <e-mail> ppliber@csk.am.lodz.pl
Abstract
Prion diseases appear as sporadic, inherited or acquired by an infection^'^.
In the inherited (familial) prion diseases over 20 point and insertional mu- tations were described, whereas in sporadic and acquired forms codon 129 homozygosity of the PRNP gene acts as a susceptibility factor. The eti- ology of sporadic CJD (sCJD) cases remains obscure. It is supposed that the expression level of prion protein gene may modulate susceptibility to sCJD. This idea comes from the results of the experiments with trans- genic mice with additional Pmp copies. These mice show shorter incuba- tion period after challenge with scrapie in comparison with that of with wild type mice. The level of prion protein expression depends on the PRNP gene regulatory elements; thus we suppose that polymorphisms in the regulatory region of the PRNP gene may be a risk factor for sCJD.
In presented study, we subjected 45 sCJD cases and 117 healthy indi- viduals to the sequencing of the PRNP promoter region polymorphisms.
The C to G transversion at position -101 was found among sCJD and con- trol group with -lOlG allele frequency 0.14 and 0.16, respectively. We found that -lOlG polymorphism is overrepresented among sCJD 129MV heterozygous cases compared with the control group (0.53 vs. 0.27; P = 0.0452). We observed no difference in the -lOlG allele frequency be- tween 129MM homozygous sCJD and control groups. We conclude that the presence of-lOlG allele significantly reduces the protective effect of
129MV heterozygosity. This data suggests that polymorphism in the regulatory region of PRNP gene may influence the susceptibility to sCJD.
This study is supported by EC NeuroPrion Network of Excellence.
223
224
