Pediatric Rheumatology Online Journal → July 2003 → Childhood Lupus→ Immunology and Immunogenetics → Abstract #86

BIOPSY-PROVEN VASCULITIS IS RELATED TO GENETIC LINKAGES AT 1P36 AND 3P13 IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

A. L. Sestak,¹ B. Namjou,¹ J. Kilpatrick,¹ J. A. Kelly,¹ T. Aberle,¹ T. Lam,¹ J. Reid,¹ J. Wilson,² R. P. Kimberly,³ T. T. Provost,⁴ J. A. James,¹ J. B. Harley.¹

¹Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK; ²University of Mississippi, Jackson, MS; ³University of Alabama at Birmingham, Birmingham, AL; ⁴Johns Hopkins University, Baltimore, MD

We have recently screened 196 pedigrees multiplex for SLE at 307 microsatellite markers distributed throughout the genome. In an effort to concentrate particular genetic effects, we identified 21 of these pedigrees containing at least one SLE patient with biopsy-proven vasculitis and subjected this subgroup to genetic linkage using SLE as the phenotype. We were able to identify linkage effects at two loci in the entire subgroup (consisting of 13 European-American families, 4 African-American families, and 4 others), as well as in the 13 European-American families considered alone. The most significant two-point parametric LOD score was obtained at 1p36 using a recessive model with 100% penetrance and complete homogeneity (theta=0); this gave LOD=5.42 for all 21 pedigrees and LOD=5.00 for the 13 European-American pedigrees alone. A second significant effect was obtained at 3p13 using a dominant model with 50% penetrance at 100% homogeneity (theta=0), with LOD=4.24 for all 21 pedigrees together. Multipoint LOD scores and heterogeneity LOD scores (HLOD) were computed using the same models described above. The 13 European-American pedigrees produced HLOD=4.02 at 1p36 between D1s1612 and D1s552, a 10.5-cM interval, with the peak at 19.2 cM (NPL score =2.41, p0.01, alpha=0.77). The entire subgroup of 21 pedigrees produced LOD=3.70 at 3p13, between D3s1766 and D3s2459, a 32 cM interval, with the peak at 108 cM (NPL score=3.21, P0.001, alpha=1.00). The two powerful linkage signals found in this subgroup of families selected for vasculitis provides additional evidence of the complex genetic interactions at work in SLE and may implicate genes potentially important in mediating vascular inflammation in these patients.