Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

Matthew T Bishop¹ , Gabor G Kovacs² , Pascual Sanchez-Juan³^,4 and Richard SG Knight¹

¹National CJD Surveillance Unit, Bryan Matthews Building, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

²Institute of Neurology, Medical University Vienna, Vienna, Austria

³Institute for Formation and Research of the Fundación "Marqués de Valdecilla" (IFIMAV), Santander, Spain

⁴Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)

author email corresponding author email

BMC Medical Genetics 2008, 9:31doi:10.1186/1471-2350-9-31


Published:	21 April 2008

Abstract

Background

Variant Creutzfeldt-Jakob disease (vCJD) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE) material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571) previously examined in Alzheimer's disease (AD).

Methods

Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression.

Results

There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype.

Conclusion

This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease.