Association of Systemic Lupus Erythematosus withC8orf13–BLKandITGAM–ITGAX

Abstract

We identified and then confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region.

Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese

“…The haplotype marked by rs7574865 was found to be present on 31% of chromosomes of SLE patients but only on 22% of those in controls (odds ratio (OR) ¼ 1.55, P ¼ 1.87 Â 10 À9 ). 5 This association was replicated by Hom et al 7 with 341 added cases and 2905 added controls from the study of Remmers et al Association of STAT4 with SLE was also confirmed in several other studies. [8][9][10] SNP rs7574865 was found to be associated with lupus nephritis, ds-DNA antibody production and age of onset.…”

“…The two SNPs have moderate LD to each other, with r 2 equals 0.39 and 0.57 in Caucasians and Chinese, respectively. The strong association of rs13277113 in BLK with SLE in Chinese is not surprising, as the study by Hom et al 7 has shown that this SNP is associated with BLK expression in both Asians (Chinese and Japanese) and Caucasians. Stratification on subphenotypes on this gene did not show any significant differences (data not shown).…”

“…The risk allele was also found to be related with reduced expression of BLK and increased expression of C8orf13, a gene 25 kb away from this SNP on the opposite strand. 7 Association of BLK with SLE was also confirmed by the study of Harley et al 8 on SNPs rs2248932 (OR ¼ 1.22, P ¼ 7 Â 10 À10 ) and rs10903340 (OR ¼ 1.18, P ¼ 1.46 Â 10 À7 ). For the latter study, association on SNP rs13277113 was not directly examined.…”

“…11,12 In the GWA study by Hom et al, 7 rs7574865 in STAT4 showed highly significant association with SLE risk, with a P-value only second to variants in the human leukocyte antigen locus. In addition to rs7574865, both Harley et al 8 and Hom et al 7 showed that rs7601754 was also significantly associated with SLE. Although the P-values for this SNP were less significant than those found for rs7574865, the association was not readily explained by its LD with rs7574865, because the r 2 value between the two is low in Caucasians according to HapMap data.…”

“…[2][3][4] Recent work on genome-wide association (GWA) studies has discovered several novel susceptibility genes for SLE, including STAT4, BLK, PXK, ITGAM, BANK1 and a few others. [5][6][7][8] However, these studies were mainly conducted on populations of European ancestry, and it is important to examine whether those genes are also risk factors for populations of other origins. Using 910 SLE patients and 1440 controls of Chinese ethnicity living in Hong Kong, as well as a case-control sample collection in Thailand, we examined some of the newly discovered susceptibility genes in our populations by genotyping the single nucleotide polymorphisms (SNPs) that showed the highest significance in association with the disease in the reported studies, but without high linkage disequilibrium (LD) to each other.…”