Title: Chromosome 7q21-22 and multiple sclerosis: evidence for a genetic susceptibility effect in vicinity to the protachykinin-1 gene
Authors: Vandenbroeck, Koen ×
Fiten, Pierre
Heggarty, Shirley
Goris, An
Cocco, Eleonora
Hawkins, Stanley A
Graham, Colin A
Marrosu, Maria G
Opdenakker, Ghislain #
Issue Date: Apr-2002
Series Title: Journal of neuroimmunology vol:125 issue:1-2 pages:141-8
Abstract: Chromosome 7q21-22 and, in particular, the region surrounding D7S554 emerged from the recent American genome screen in multiple sclerosis (MS) as the most promising region genome-wide for harboring a disease susceptibility gene. We tested association between D7S554 and MS in 217 Sardinian trio MS families by the transmission disequilibrium test (TDT), and in a Northern Irish case-control study comprising 542 individuals. In both populations, we found evidence for significant allelic association (P(c)=0.04 and P(c)=0.0002, respectively). In a second stage, we analysed five microsatellite markers in a 4 megabase interval on chromosome 7q21-22 in the same set of Sardinian families. Parental transmission of a single allele of one of these markers, i.e. D7S3126, was significantly distorted (P(c)=0.008). D7S554 and D7S3126 are located at distances of, respectively, 40 and 81 kb 5' from the startcodon of the protachykinin-1 gene (TAC1), and occur in strong linkage disequilibrium (P<10(-7)). Our study indicates that the previous finding of linkage with D7S554 refers possibly to the presence of an MS susceptibility effect in vicinity to TAC1. In addition, a second independent association was uncovered between a microsatellite polymorphism in the plasminogen activator inhibitor-1 gene, i.e. D7S477, and MS. Overall, the analysis presented here may contribute to the increasingly refined genomic map of MS and underscores the requirement for a further high-resolution screening of chromosome 7q21-22.
ISSN: 0165-5728
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Laboratory of Immunobiology (Rega Institute)
Laboratory for Neuroimmunology
× corresponding author
# (joint) last author

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