Haplotype analysis of the preprotachykinin-1 (TAC1) gene in multiple sclerosis.
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. Genes and Immunity (2005) 6, 265-270. doi:10.1038/sj.gene.6364175 Published online 24 February 2005.
Cunningham
S
S
Applied Genomics Research Group, School of Pharmacy, Queen's University of Belfast, Belfast, UK.
Patterson
C C
CC
McDonnell
G
G
Hawkins
S
S
Vandenbroeck
K
K
D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008957:Models, Genetic; D009103:Multiple Sclerosis / Q000235:genetics*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics*
D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin