No evidence for association between taugene haplotypic variants and susceptibility to Creutzfeldt-Jakob disease

Pascual Sánchez-Juan,Alejandro Arias-Vasquez,Anna Poleggi,Claudia Giannattasio,Richard Sg Knight,Cornelia M Van Duijn,Alison Green,Matthew T Bishop

doi:10.1186/1471-2350-8-77

Abstract

BackgroundA polymorphism at codon 129 of the prion protein gene (PRNP) is the only well-known genetic risk factor for Creutzfeldt-Jakob disease (CJD). However, there is increasing evidence that other loci outside the PRNP open reading frame might play a role in CJD aetiology as well.MethodsWe studied tau protein gene (MAPT) haplotypic variations in a population of sporadic and variant CJD patients. We tested 6 MAPT haplotype tagging SNPs (htSNPs) in a Dutch population-based sample of sporadic CJD (sCJD) patients and a cognitively normal control group of similar age distribution. We genotyped the same polymorphisms in two other sample groups of sCJD cases from Italy and the UK. In addition, we compared MAPT haplotypes between sCJD and variant CJD (vCJD) patients.ResultsSingle locus and haplotype analyses did not detect any significant difference between sCJD cases and controls. When we compared MAPT haplotypes between sCJD and variant CJD (vCJD) patients, we found that two of them were represented differently (H1f: 8% in sCJD versus 2% in vCJD; H1j:1% in sCJD versus 7% in vCJD). However, these two haplotypes were rare in both groups of patients, and taking the small sample sizes into account, we cannot exclude that the differences are due to chance. None of the p-values remained statistically significant after applying a multiple testing correction.ConclusionOur study shows no evidence for an association between MAPT gene variations and sCJD, and some weak evidence for an association to vCJD.

Highlights

A polymorphism at codon 129 of the prion protein gene (PRNP) is the only wellknown genetic risk factor for Creutzfeldt-Jakob disease (CJD)
Neurofibrillary tangles (NFTs) are present in other neurodegenerative diseases, including progressive supranuclear palsy (PSP), cortico basal degeneration (CBD), Pick's disease, and argyrophilic grain disease and Parkinson's disease (PD) [1,2,3,4]
In the present study we examined the association between Methods: We studied tau protein gene (MAPT) haplotypic variants and risk of sporadic CJD (sCJD) and variant CJD (vCJD)

Summary

Introduction

A polymorphism at codon 129 of the prion protein gene (PRNP) is the only wellknown genetic risk factor for Creutzfeldt-Jakob disease (CJD). There is increasing evidence that other loci outside the PRNP open reading frame might play a role in CJD aetiology as well. Tau protein plays a key role in the pathogenesis of several neurodegenerative disorders. In patients with sporadic CJD, the tau protein is profusely released to the CSF [5]. This process is most likely related to the rapid neuronal damage. In contrast to sCJD, in vCJD there is an increase of phosphorylated-tau forms in CSF [7]. The pathogenic implications of this finding are unknown, but it suggests that tau phosphorylation may differ between sCJD and vCJD

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Conclusion