title: PECAM1, MPO and PRKAR1A at chromosome 17q21-q24 and susceptibility for multiple sclerosis in Sweden and Sardinia.
abstract: Using genome screen, DNA sequence and mapping data, we scanned the human chromosomal region 17q21-q24 for polymorphic markers in single copy genes. Three such genes were identified: the gene for myeloperoxidase (MPO) at 17q21.3-q23.2, containing a CA-microsatellite in the eighth intron and a functional single base substitution (G to A) in the promoter region, the platelet endothelial cell adhesion molecule-1 gene (PECAM1) at 17q23, which has a CA-repeat sequence in the sixth intron, and the gene for the regulatory subunit RIalpha of cAMP-dependent protein kinase (PRKAR1A) at 17q23-q24, in which a GA-microsatellite was detected in the 5'-flanking region. Association of these polymorphisms with multiple sclerosis (MS) was studied in a Swedish case-control population of 199 MS patients and 145 control subjects, and in 203 simplex families from Sardinia. None of these polymorphic genes was found to be a genetic marker for disease susceptibility. These results are in contrast with previous studies on the involvement of MPO in MS and suggest that the elevated expression of PECAM-1 in MS, as earlier documented, is related to transactivation by other gene products.
authors.affiliation: Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Nelissen
authors.forename: P
authors.initials: P
authors.lastname: Fiten
authors.forename: K
authors.initials: K
authors.lastname: Vandenbroeck
authors.forename: J
authors.initials: J
authors.lastname: Hillert
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: M G
authors.initials: MG
authors.lastname: Marrosu
authors.forename: G
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics*; D010641:Phenotype; D020161:Physical Chromosome Mapping; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D013548:Sweden
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D009195:Peroxidase; D017868:Cyclic AMP-Dependent Protein Kinases