1. ¹Applied Genomics Research Group, School of Pharmacy, Queen's University of Belfast, Belfast, UK
2. ²Department of Epidemiology and Public Health, School of Medicine, Queen's University of Belfast, Belfast, UK
3. ³Neurology Department, Royal Victoria Hospital, Belfast, UK

Correspondence: Professor K Vandenbroeck, Applied Genomics Research Group, McClay Research Center, Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. E-mail: k.vandenbroeck@qub.ac.uk

Received 4 October 2004; Revised 10 January 2005; Accepted 12 January 2005; Published online 24 February 2005.

Abstract

The potential relevance of chromosome 7q21–22 in susceptibility to multiple sclerosis (MS) has been highlighted in genome-wide linkage screens as well as in association studies of 7q-specific polymorphic microsatellites. Especially, recent, independently performed studies have provided evidence for significant association of the markers D7S554 and D7S3126 with MS in Sardinian, Northern Irish and Spanish–American cohorts. The gene most closely located to these markers is the neuropeptide preprotachykinin-1 (TAC1) gene. Both its position and the array of biological functions exerted by its expression products make it a logical primary choice for further scrutiny as the putative chromosome 7q21–22 MS susceptibility gene. We report identification of eight polymorphisms in this gene by means of a sequencing approach. A Northern Irish case–control was typed for six of these polymorphisms. One of these, an intron 1 single-nucleotide polymorphism (SNP), showed significant association with MS (P=0.009). Two-marker haplotypes composed of allelic combinations of TAC1 promoter–intron 1 SNPs were highly significantly associated with MS and more so with the relapsing-remitting form of this disease. While independent reproduction of these data in other data sets is indicated, our work is suggestive for a role of the TAC1 gene in MS.