Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in families with vitiligo-related systemic lupus erythematosus

Abstract

Both systemic lupus erythematosus (SLE) and vitiligo are autoimmune disorders that have strong evidence of complex genetic contributions to their etiology, but, to date, efforts using genetic linkage to find the susceptibility genes for either phenotype have met with limited success. Since autoimmune diseases are thought to share at least some of their genetic origins, and since only a small minority (16 of 92) of the European-American pedigrees multiplex for SLE in our collection have one or more affected members with vitiligo, we hypothesized that these pedigrees might be more genetically homogeneous at loci important to both SLE and vitiligo and, hence, have increased power for detection of linkage. We therefore evaluated genomewide microsatellite-marker-scan data for markers at an average marker density of approximately 11 cM in these 16 European-American pedigrees and identified a significant linkage at 17p13, where the maximum multipoint parametric LOD score was 3.64 (P<4.3x10(-5)) and the nonparametric linkage score was 4.02 (P<2.8x10(-5)), respectively. The segregation behavior of this linkage suggests a recessive mode of inheritance with a virtually homogeneous genetic effect in these 16 pedigrees. These results support the hypotheses that SLE and vitiligo may share important genetic effects and that sampling on the basis of clinical covariates dramatically improves power to identify genetic effects.

Figure 1

Multipoint model-free (Z_lr score) and model-based (LOD score) linkage, for chromosome 17 in families with vitiligo-related SLE. Marker positions are denoted by the vertical tic marks; the marker order, from left to right, is D17S1303-D17S1998-D17S974-D17S1303-D17S2196-D17S1294-D17S1299-D17S2180-D17S1290-D17S2193-D17S1301-D17S784-D17S928.