The gene for the prion protein has been identified and examination of it reveals a common polymorphism at codon 129 for either methionine or valine. This has relevance to both iatrogenic and sporadic forms of prion disease.
In the caucasian population approximately 38% are homozygous for methionine alleles, 51% are heterozygous and 11% are homozygous for valine.
- in all cases of CJD, including sporadic CJD, there is an overrepresentation of homozygosity at the polymorphic codon 129 of the prion protein gene
- in sporadic CJD
- approximately 85% of the patients are homozygous at codon 129, compared to about 50% in the general population in Europe, among whom two thirds are genotype methionine homozygous (Met/Met), indicating that homozygotes have a higher risk of developing CJD compared to heterozygotes
- in iatrogenic CJD
- in CJD caused by cadaveric pituitary human growth hormone the overrepresentation is due to the val/val genotype (31% compared to approximately 11% of the normal population) and not to the methionine homozygosity (Met/Met) seen in most other cases of CJD
- codon 129 methionine homozygosity has been found in 74% of patients with CJD caused by dura mater grafts
Reference:
- Pedersen NS, Smith E. Prion diseases: epidemiology in man. APMIS. 2002 Jan;110(1):14-22.