Prion protein codon 129 polymorphism in mild cognitive impairment and dementia: the Rotterdam Study
BRAIN COMMUNICATIONS
Authors: Karamujic-Comic, Hata; Ahmad, Shahzad; Lysen, Thom S.; Heshmatollah, Alis; Roshchupkin, Gennady, V; Vernooij, Meike W.; Rozemuller, Annemieke J. M.; Ikram, Mohammad Arfan; Amin, Najaf; van Duijn, Cornelia M.
Abstract
Creutzfeldt-Jakob disease is a rare, fatal, neurodegenerative disease caused by the accumulation of abnormally folded prion proteins. The common polymorphism at codon 129 (methionine/valine) in the prion protein (PRNP) gene is the most important determinant of genetic susceptibility. Homozygotes of either allele have a higher risk of sporadic Creutzfeldt-Jakob disease. Various studies suggest that this polymorphism is also involved in other forms of dementia. We studied the association between the codon 129 polymorphism of the PRNP gene and mild cognitive impairment in 3605 participants from the Rotterdam Study using logistic regression analyses. Subsequently, we studied the association between this polymorphism and incident dementia, including Alzheimer's disease, in 11 070 participants using Cox proportional hazard models. Analyses were adjusted for age and sex. We found the prevalence of mild cognitive impairment to be higher for carriers of the methionine/methionine genotype (odds ratio, 1.40; 95% confidence interval, 1.11-1.78; P = 0.005) as well as for carriers of the valine/valine genotype (odds ratio, 1.37; 95% confidence interval, 0.96-1.97; P = 0.08). The codon 129 polymorphism was not associated with the risk of incident dementia or Alzheimer's disease. In conclusion, we found a statistically significant higher prevalence of mild cognitive impairment in carriers of the methionine/methionine genotype in the codon 129 polymorphism of the PRNP gene within this population-based study. No associations were found between the codon 129 polymorphism and dementia or Alzheimer's disease in the general population.
Potential scrapie-associated polymorphisms of the prion protein gene (PRNP) in Korean native black goats
SCIENTIFIC REPORTS
Authors: Kim, Seon-Kwan; Kim, Yong-Chan; Won, Sae-Young; Jeong, Byung-Hoon
Abstract
Small ruminants, including sheep and goats are natural hosts of scrapie, and the progression of scrapie pathogenesis is strongly influenced by polymorphisms in the prion protein gene (PRNP). Although Korean native goats have been consumed as meat and health food, the evaluation of the susceptibility to scrapie in these goats has not been performed thus far. Therefore, we investigated the genotype and allele frequencies of PRNP polymorphisms in 211 Korean native goats and compared them with those in scrapie-affected animals from previous studies. We found a total of 12 single nucleotide polymorphisms (SNPs) including 10 nonsynonymous and 2 synonymous SNPs in Korean native goats. Significant differences in allele frequencies of PRNP codons 143 and 146 were found between scrapie-affected goats and Korean native goats (p < 0.01). By contrast, in PRNP codons 168, 211 and 222, there were no significant differences in the genotype and allele frequencies between scrapie-affected animals and Korean native goats. To evaluate structural changes caused by nonsynonymous SNPs, PolyPhen-2, PROVEAN and AMYCO analyses were performed. PolyPhen-2 predicted "possibly damaging" for W102G and R154H, "probably damaging" for G127S. AMYCO predicted relatively low for amyloid propensity of prion protein in Korean native black goats. This is the first study to evaluate the scrapie sensitivity and the first in silico evaluation of nonsynonymous SNPs in Korean native black goats.