Our data revealed that TLR stimulation of PBC (n = 17) and pSS monocytes (n = 6) resulted in significant induction of IL12A mRNA (p < 0.05, p < 0.01, respectively) compared to PSC monocytes (n = 13) and at similar levels to HC monocytes (n = 8).
In addition, the risk alleles of the 2 SNPs were significantly associated with down-regulation of SCHIP1, a celiac disease susceptible gene, 91.5 kb upstream of IL12A.These results not only demonstrated that IL12A is associated with PBC in the Chinese Han population but also identified a potential mechanism for its involvement in the pathogenesis of PBC.
Here, we performed an association analysis between IL12A, IL12RB, and signal transducer and activator of transcription 4 (STAT4) genetic variations and susceptibility to PBC.
Fine-mapping analysis showed that a five-allele haplotype in the 3' flank of IL12A was significantly associated with primary biliary cirrhosis (P=1.15x10(-34)).
We fine mapped two primary biliary cirrhosis (PBC) risk loci, CLEC16A (C-type lectin domain family 16 member A)-suppressor of cytokine signaling 1 (SOCS1) and Spi-B protein (SPIB) and sequenced a locus, sialic acid acetylesterase (SIAE), proposed to harbor autoimmunity-associated mutations.
To examine the genetics of susceptibility to primary biliary cirrhosis (PBC), genome-wide association studies GWAS have been performed in patients of European ancestry and have shown the significant associations of IL12-related pathways, SPIB, IRF5-TNPO3, and 17q12-21.
<i>Background</i>.Recent GWAS in primary biliary cholangitis (PBC) showed strong associations with SNPs located within interleukin-12 receptor (IL12R) beta-2 <i>(IL12RB2)</i> gene.<i>Aims</i>.
Here, we performed an association analysis between IL12A, IL12RB, and signal transducer and activator of transcription 4 (STAT4) genetic variations and susceptibility to PBC.
Double immunofluorescence labeling with a canalicular marker (dipeptidyl peptidase IV) demonstrated proper canalicular localization of BSEP and MRP2 in PBC.
We investigated the uptake transporters OATP2 (SLC21A6), OATP8 (SLC21A8), and NTCP (SLC10A1), the export pumps MRP2 (ABCC2), MRP3 (ABCC3), MRP6 (ABCC6), and P-glycoproteins (ABCB1, ABCB4, ABCB11), and radixin, in non-icteric primary biliary cirrhosis (PBC stages I-III) and control human liver needle-biopsies using immunofluorescence microscopy and semi-quantitative RT-PCR.