Lack of association between PRNP 1368 polymorphism and Alzheimer's disease or vascular dementia.
BACKGROUND
Polymorphisms of the prion protein gene (PRNP) at codons 129 and 219 play an important role in the susceptibility to Creutzfeldt-Jakob disease (CJD), and might be associated with other neurodegenerative disorders. Several recent reports indicate that polymorphisms outside the coding region of PRNP modulate the expression of prion protein and are associated with sporadic CJD, although other studies failed to show an association. These reports involved the polymorphism PRNP 1368 which is located upstream from PRNP exon 1. In a case-controlled protocol, we assessed the possible association between the PRNP 1368 polymorphism and either Alzheimer's disease (AD) or vascular dementia (VaD).


METHODS
To investigate whether the PRNP 1368 polymorphism is associated with the occurrence of AD or VaD in the Korean population, we compared the genotype, allele, and haplotype frequencies of the PRNP 1368 polymorphism in 152 AD patients and 192 VaD patients with frequencies in 268 healthy Koreans.


CONCLUSIONS
Significant differences in genotype, allele and haplotype frequencies of PRNP 1368 polymorphism were not observed between AD and normal controls. There were no significant differences in the genotype and allele frequencies of the PRNP 1368 polymorphism between Korean VaD patients and normal controls. However, in the haplotype analysis, haplotype Ht5 was significantly over-represented in Korean VaD patients. This was the first genetic association study of a polymorphism outside the coding region of PRNP in relation to AD and VaD.
Jeong
Byung-Hoon
BH
Ilsong Institute of Life Science, Hallym University, Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do, South Korea. bhjeong@hallym.ac.kr
Lee
Kyung-Hee
KH
Lee
Yun-Jung
YJ
Kim
Yun Joong
YJ
Choi
Eun-Kyoung
EK
Kim
Young-Hoon
YH
Cho
Young-Sook
YS
Carp
Richard I
RI
Kim
Yong-Sun
YS
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003062:Codon; D015140:Dementia, Vascular / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*
D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions