Fine mapping chromosome 16q12 in a collection of 231 systemic lupus erythematosus sibpair and multiplex families

Abstract

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder influenced by multiple genetic and environmental factors. Linkage of SLE to chromosome 16q12-13 (LOD score ¼ 3.85) was first identified in pedigrees collected at the University of Minnesota, and has been replicated in several independent SLE collections. We performed fine mapping using microsatellites to further refine the susceptibility region(s), and the best evidence for linkage was identified at marker D16S3396 (LOD ¼ 2.28, P ¼ 0.0006). Evidence of association was suggested in the analysis of all families (D16S3094, P ¼ 0.0516) and improved to the level of significance (P ¼ 0.0106) when only the Caucasian families were analyzed. Subsets of pedigrees were then selected on the basis of clinical manifestations, and these subsets showed evidence for association with several markers: GATA143D05 (renal, P ¼ 0.0064), D16S3035 (renal, P ¼ 0.0418), D16S3117 (renal, P ¼ 0.0366), D16S3071 (malar rash, P ¼ 0.03638; neuropsychiatric, P ¼ 0.0349; oral ulcers, P ¼ 0.0459), D16S3094 (hematologic, P ¼ 0.0226), and D16S3089 (arthritis, P ¼ 0.0141). Together, these data provide further evidence that an important susceptibility gene(s) for SLE is located at 16q12.

Olf1/EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus

“…Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with relatively strong genetic components that genome wide linkage scans performed in the past decade have identified chromosome 16p12.3 to q12.2 to be the second-strongest locus linked to SLE after HLA (6p22.3 to 6p21.1) [1-8]. A positional candidate gene, ITGAM located at 16p11.2, has been recently identified and validated as a lupus susceptibility gene by different groups [9-11].…”

“…A positional candidate gene, ITGAM located at 16p11.2, has been recently identified and validated as a lupus susceptibility gene by different groups [9-11]. However, fine mapping experiments of the chromosome 16p locus have shown multiple association signals clustering in several regions [8,12], suggesting more than one gene may be involved in the increased risk of SLE.…”

Fine-Mapping Chromosome 20 in 230 Systemic Lupus Erythematosus Sib Pair and Multiplex Families: Evidence for Genetic Epistasis with Chromosome 16q12

“…[6][7][8][9][10][11] Linkage studies in human SLE pedigrees have identified multiple regions that meet genomewide criteria for significant or suggestive linkage, 12 which is consistent with the hypothesis that SLE is a complex polygenic disease. [13][14][15][16][17][18][19][20][21][22][23][24][25][26] Our group was one of the first to provide evidence for linkage on chromosome 20 (D20S186, LOD p ) in an initial study of 105 SLE sib pair pedigrees. 15…”

Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis

“…At least four independent study groups reported the evidence of SLE linkage in this region. Recently, two independent replication studies confirmed this linkage (Nath et al 2004a, b;Gillett et al 2005). Interestingly, a Chinese group using a familybased association test, found an association between OAZ gene at 16q12 and SLE in Chinese population (Feng et al 2003(Feng et al , 2004.…”