Evidence for linkage of a candidate chromosome I region to human systemic lupus erythematosus
Journal
Journal of Clinical Investigation
Journal Volume
99
Journal Issue
4
Pages
725-731
Date Issued
1997
Author(s)
Tsao B.P.
Cantor R.M.
Kalunian K.C.
Chen C.-J.
Badsha H.
Singh R.
Wallace D.J.
Kitridou R.C.
Chen S.-L.
Shen N.
Song Y.W.
Isenberg D.A.
Hahn B.H.
Rotter J.I.
Abstract
Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs 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 evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups.
SDGs
Publisher
American Society for Clinical Investigation
Type
journal article