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

Pascual Sánchez-Juan¹^,2^,3 , Matthew T Bishop⁴ , Alison Green⁴ , Claudia Giannattasio⁵ , Alejandro Arias-Vasquez² , Anna Poleggi⁵ , Richard SG Knight⁴ and Cornelia M van Duijn²

¹Institute for Formation and Research of the Fundación "Marqués de Valdecilla" (IFIMAV), Santander, Spain

²Genetic Epidemiology Unit, Epidemiology & Biostatistics department, Erasmus MC, Rotterdam, The Netherlands

³Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)

⁴National CJD Surveillance Unit, The University of Edinburgh, EH4 2XU Edinburgh, UK

⁵Istituto Superiore di Sanità, Laboratory of Virology, Viale Regina Elena 299, 00161 Rome, Italy

author email corresponding author email

BMC Medical Genetics 2007, 8:77doi:10.1186/1471-2350-8-77


Published:	11 December 2007

Abstract

Background

A 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.

Methods

We 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.

Results

Single 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.

Conclusion

Our study shows no evidence for an association between MAPT gene variations and sCJD, and some weak evidence for an association to vCJD.