Creutzfeldt-Jakob disease risk and PRNP codon 129 polymorphism: necessity to revalue current data
E Mitrová1, V Mayer, V Jovankovicová
1Department of Prion Diseases, Institute of Preventive and Clinical Medicine, Research Base of Slovak Medical University, Bratislava, Slovak Republic. eva.mitrova@szu.edu
European Journal of Neurology
|December 6, 2005
Summary
The prion protein gene (PRNP) codon 129 polymorphism (M129V) influences Creutzfeldt-Jakob disease (CJD) risk. This study reveals a higher prevalence of methionine homozygotes in corneal donors, highlighting the need to re-evaluate CJD reference data.
Area of Science:
- Genetics
- Neuroscience
- Epidemiology
Background:
- The prion protein gene (PRNP) codon 129 polymorphism (M129V) is a key genetic factor for Creutzfeldt-Jakob disease (CJD) susceptibility in Caucasians.
- Previous studies on M129V distribution in healthy populations, often using small sample sizes, suggested methionine/valine heterozygosity as the most frequent genotype.
- Recent investigations indicate potential discrepancies with these earlier findings, necessitating updated reference data.
Purpose of the Study:
- To analyze the distribution of the PRNP codon 129 M129V polymorphism in a large cohort of healthy corneal donors.
- To compare these findings with existing reference data and investigate potential demographic influences (age, gender) on genotype frequencies.
- To assess the implications for CJD risk evaluation and the necessity of revising current reference data.
Main Methods:
- Genotyping analysis of the PRNP codon 129 M129V polymorphism.
- Statistical analysis of genotype frequencies in 613 corneal donors.
- Comparison of observed genotype distribution with previous studies and assessment of gender and age-related differences.
Main Results:
- Methionine homozygotes (48.1%) were the most prevalent genotype, followed by methionine/valine heterozygotes (43.2%) and valine homozygotes (8.7%).
- No significant age-related differences in genotype distribution were observed.
- A statistically significant difference in M129V genotype distribution was found between genders.
Conclusions:
- The M129V genotype distribution in this large corneal donor cohort differs from previously established reference data, with a higher proportion of methionine homozygotes.
- The significant gender-based difference underscores the importance of considering sex in M129V genotype analysis.
- These findings necessitate a re-evaluation of the generally accepted reference data for M129V, incorporating gender, age, and geographical factors for accurate CJD risk assessment.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...