EVIDENCE FOR LINKAGE OF A CANDIDATE CHROMOSOME-1 REGION TO HUMAN SYSTEMIC LUPUS-ERYTHEMATOSUS

Genetic susceptibility confers significant risk for systemic lupus ery thematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involveme nt of a genetic locus includes linkage, we tested a candidate region h omologous to a murine SLE susceptibility region in 52 SLE-affected sib pairs from three ethnic groups. We analyzed seven microsatellite marke rs from the human chromosome 1q31-q42 region corresponding to the telo meric end of mouse chromosome 1, the region where specific manifestati ons of murine lupus, including glomerulonephritis and IgG antichromati n, have been mapped. Comparing the mean allele sharing in affected sib pairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evid ence for linkage to two of these five markers (P = 0.04), suggesting t hat this phenotype is conserved between mice and humans. Compared to t he expected random distribution, the trend of increased sharing of hap lotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably con tains a susceptibility gene(s) that confers risk for SLE in multiple e thnic groups.