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Research Article Free access | 10.1172/JCI119217

Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus.

B P Tsao, R M Cantor, K C Kalunian, C J Chen, H Badsha, R Singh, D J Wallace, R C Kitridou, S L Chen, N Shen, Y W Song, D A Isenberg, C L Yu, B H Hahn, and J I Rotter

University of California, Los Angeles, USA. btsao@med1.medsch.ucla.edu

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Published February 15, 1997 - More info

Published in Volume 99, Issue 4 on February 15, 1997
J Clin Invest. 1997;99(4):725–731. https://doi.org/10.1172/JCI119217.
© 1997 The American Society for Clinical Investigation
Published February 15, 1997 - Version history
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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.

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