Open Access Research article

A polymorphism in the regulatory region of PRNP is associated with increased risk of sporadic Creutzfeldt-Jakob disease

Pascual Sanchez-Juan12*, Matthew T Bishop3, Esther A Croes4, Richard SG Knight3, Robert G Will3, Cornelia M van Duijn5 and Jean C Manson6

Author Affiliations

1 Neurology Department, University Hospital "Marqués de Valdecilla" and CIBERNED, Santander, Spain

2 Research Institute "Marqués de Valdecilla" (IFIMAV). Santander. Spain

3 The National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK

4 Trimbos-institute, Utrecht, The Netherlands

5 Genetic Epidemiology Unit, Department of Epidemiology & Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands

6 Neuropathogenesis Division, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, UK

For all author emails, please log on.

BMC Medical Genetics 2011, 12:73  doi:10.1186/1471-2350-12-73

Published: 22 May 2011



Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. An important determinant for CJD risk and phenotype is the M129V polymorphism of the human prion protein gene (PRNP), but there are also other coding and non-coding polymorphisms inside this gene.


We tested whether three non-coding polymorphism located inside the PRNP regulatory region (C-101G, G310C and T385C) were associated with risk of CJD and with age at onset in a United Kingdom population-based sample of 131 sporadic CJD (sCJD) patients and 194 controls.


We found no disease association for either PRNP C-101G or PRNP T385C. Although the crude analysis did not show a significant association between PRNP G310C and sCJD (OR: 1.5; 95%CI = 0.7 to 2.9), after adjusting by PRNP M129V genotype, it resulted that being a C allele carrier at PRNP G310C was significantly (p = 0.03) associated with a 2.4 fold increased risk of developing sCJD (95%CI = 1.1 to 5.4). Additionally, haplotypes carrying PRNP 310C coupled with PRNP 129M were significantly overrepresented in patients (p = 0.02) compared to controls. Cases of sCJD carrying a PRNP 310C allele presented at a younger age (on average 8.9 years younger than those without this allele), which was of statistical significance (p = 0.05). As expected, methionine and valine homozygosity at PRNP M129V increased significantly the risk of sCJD, alone and adjusted by PRNP G310C (OR MM/MV = 7.3; 95%CI 3.9 to 13.5 and OR VV/MV = 4.0; 95%CI 1.7 to 9.3).


Our findings support the hypothesis that genetic variations in the PRNP promoter may have a role in the pathogenesis of sCJD.

Creutzfeldt-Jakob disease; prion protein gene; molecular subtype; regulatory region; early onset