Systemic Lupus Erythematosus, Susceptibility To, 12

For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.

Mapping

Hom et al. (2008) performed a genomewide association study involving more than 500,000 SNPs in DNA samples from 1,311 case subjects with SLE and 1,783 control subjects; all subjects were North Americans of European descent. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden. The A allele of a single-nucleotide polymorphism on chromosome 8p23.1, rs13277113, was highly enriched in the sample from United States case subjects as compared with controls (P = 8 x 10(-8); combined OR, 1.39; 95% CI, 1.26-1.54). An association was also observed in the Swedish replication set (P = 4 x 10(-4); OR, 1.33; 95% CI, 1.13-1.55). A combined analysis of rs13277113 with both the United States and Swedish samples showed P = 1 x 10(-10). The SNP rs13277113 maps to the interval between 2 genes transcribed in opposite directions: BLK (191305), a tyrosine kinase in the Src family that signals downstream of the B cell receptor, and C8ORF13 (FAM167A; 610085). Homozygotes for the A allele of rs13277113 had levels of BLK mRNA expression that were approximately 50% of those of homozygotes for the G allele. The expression of the C8ORF13 gene also correlated with the rs13277113 SNP, but in the opposite direction. The A allele was associated with higher expression of C8ORF13, whereas the G allele was significantly associated with lower expression. A/G heterozygotes had intermediate levels of expression of both genes.

Han et al. (2009) performed a genomewide association study of SLE in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina-Human610-Quad BeadChips and replicating 78 SNPs in 2 additional cohorts (3,152 cases and 7,050 controls). Han et al. (2009) found association with 3 SNPs at the BLK gene. The strongest association was with rs7812879 (combined P value = 2.09 x 10(-24), odds ratio = 0.69, 95% confidence interval 0.64-0.74).