PECAM1, MPO and PRKAR1A at chromosome 17q21-q24 and susceptibility for multiple sclerosis in Sweden and Sardinia

Using genome screen, DNA sequence and mapping data, we scanned the human ch romosomal region 17q21-q24 for polymorphic markers in single copy genes. Th ree such genes were identified: the gene for myeloperoxidase (MPO) at 17q21 .3-q23.2, containing a CA-microsatellite in the eighth intron and a functio nal single base substitution (G to A) in the promoter region, the platelet endothelial eel adhesion molecule-1 gene (PECAM1) at 17q23, which has a CA- repeat sequence in the sixth intron, and the gene for the regulatory subuni t Riot of cAMP-dependent protein kinase (PRKAR1A) at 17q23-q24, in which a GA:microsatellite was detected in the 5'-flanking region. Association of th ese polymorphisms with multiple sclerosis (MS) was studied in a Swedish cas e-control population of 199 MS patients and 145 control subjects, and in 20 3 simplex families from Sardinia. None of these polymorphic genes was found to be a genetic marker for disease susceptibility. These results are in co ntrast with previous studies on the involvement of MPO in MS and suggest th at the elevated expression of PECAM-1 in MS, as earlier documented, is rela ted to transactivation by other gene products. (C) 2000 Elsevier Science B. V. All rights reserved.