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Genome scan stratified by the presence of anti-double-stranded DNA (dsDNA) autoantibody in pedigrees multiplex for systemic lupus erythematosus (SLE) establishes linkages at 19p13.2 (SLED1) and 18q21.1 (SLED2)

Genes & Immunity volume 3, pages S35–S41 (2002)Cite this article

Abstract

Anti-double-stranded DNA (anti-dsDNA) is arguably one of the most specific autoantibodies in systemic lupus erythematosus (SLE). This antibody is associated with more severe SLE and with glomerulonephritis. From 196 pedigrees multiplex for SLE, we selected those that had any SLE affected positive for anti-dsDNA by the Crithidia luciliae kinetoplast imunofluorescence assay. This stratification strategy tested the hypothesis that anti-dsDNA would identify a more genetically homogeneous group of pedigrees, in which previously undetected linkage effects could be established. A genome screen data for linkage to SLE was available at 307 microsatellite markers for this selected group of 71 pedigrees: 37 European-American, 29 African-American, and five others. The most significant results were obtained at 19p13.2 (LODmax = 4.93), named SLED1, in the 37 European-American pedigrees using a dominant model with mixed penetrances (92% for females and 49% for males) at 100% homogeneity (θ = 0). A second linkage effect, SLED2, was established in the 29 African-American pedigrees at 18q21.1 (LODmax = 3.40) using a recessive model with 100% penetrance (θ = 0.1). Parametric and non-parametric multipoint analyses were performed, which provided further evidence and support of susceptibility genes residing in these regions. In conclusion, two powerful linkages have been detected with SLE based on the presence of anti-dsDNA. These findings show SLE to be a richly complicated disease phenotype that is now ripe for important new discovery through a genetic approach.

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Acknowledgements

The authors would like to thank the patients and family members who participated in this study and those who referred them to us. Ninety pedigrees (Cohorts A, B and C) were obtained from the Lupus Multiplex Registry and Repository (AR-1-2253) (see http://omrf.ouhsc.edu/lupus).

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Authors and Affiliations

  1. Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, OK, USA

    B Namjou, S K Nath, J Kilpatrick, J A Kelly, J Reid, M Reichlin, J A James & J B Harley

  2. Genetic Epidemiology Unit, OK, USA

    S K Nath & J B Harley

  3. University of Oklahoma Health Sciences Center, OK, USA

    M Reichlin, J A James & J B Harley

  4. US Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA

    J A James & J B Harley

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  1. B Namjou
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  2. S K Nath
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  3. J Kilpatrick
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  4. J A Kelly
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  5. J Reid
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  6. M Reichlin
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  7. J A James
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Correspondence to J B Harley.

Additional information

Supported by the NIH (AR12253, AI24717, AR42460, AR45231, AI31584, RR15577) and the US Department of Veterans Affairs.

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Namjou, B., Nath, S., Kilpatrick, J. et al. Genome scan stratified by the presence of anti-double-stranded DNA (dsDNA) autoantibody in pedigrees multiplex for systemic lupus erythematosus (SLE) establishes linkages at 19p13.2 (SLED1) and 18q21.1 (SLED2). Genes Immun 3 (Suppl 1), S35–S41 (2002). https://doi.org/10.1038/sj.gene.6363905

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