Identification of IL12RB1 as a Novel Systemic Sclerosis Susceptibility Locus

Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

“…Two other IL-12 pathway-related genes have been related to SSc: IL12RB1 and IL12RB2, which encode both chains of the IL-12 receptor (IL-12R). Follow-up studies of the GWAS by Radstake et al and the SSc Immunochip allowed us to the identification of these two new loci reaching the genome-wide significance level [78,79]. IL12RB2 is located nearby IL23R; however, Bossini-Castillo et al reported that the observed signal was independent from IL23R [78].…”

“…suggested that rs436857 promoter SNP was the most likely causal variant [79]. The minor allele of this SNP showed a protective effect and was located in an IL12RB1 cis-eQTL that decreased IL12RB1 expression [80,81].…”

Influence ofTYK2in systemic sclerosis susceptibility: a newlocusin the IL-12 pathway

“…Interestingly, several IL-12 pathway-related genes have been reported to be associated with SSc: IL12RB1 and IL12RB2 (both IL-12-receptor chains), IL12A (p35 subunit of IL-12) and STAT4 (the transcription factor of the IL-12 signalling axis) 3 4 8 9. Thus, the association of TYK2 with SSc reported in the present study adds another piece of evidence showing the crucial role of this IL pathway in SSc pathogenesis.…”

“…Moreover, different functional and genetic studies highlighted the special relevance of IL-12/STAT4 pathway in the disease pathophysiology 3 4 8 9. Thus, we performed a follow-up study to further investigate whether variations within this genomic region, including the three variants responsible for the association in RA and other autoimmune phenotypes, are also involved in SSc susceptibility.…”

Genetic implications in the pathogenesis of systemic sclerosis

“…Remarkably, the association of rs77583790 SNP in the intergenic locus between IL12A and SCHIP1 at 3q25, rs35677470 SNP in Deoxyribonuclease 1 Like 3 ( DNASE1L3 ) gene at 3p14, as well as rs9373839 SNP located in intronic region of ATG5 at 6q21 with ACA positivity and overall SSc risk have been demonstrated . In addition, IL12RB1 and IL12RB2 coding genes have been associated with overall SSc . The IL12RB2 ‐associated variant (rs3790567) and IL12RB1 gene rs436857 SNP were determined to be risk factors in the pathogenesis of SSc .…”