J Neuroimmunol 2002 Apr;125(1-2):141-8
Vandenbroeck K, Fiten P, Heggarty S, Goris A, Cocco E, Hawkins SA, Graham CA, Marrosu MG, Opdenakker G.
Rega Institute for Medical Research, University of Leuven, B-3000, Louvain, Belgium
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.