Biliary Cirrhosis, Primary, 4

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

IL12A, SPIB, IL12RB1, ABCC2, NOS2, MMEL1, TNFSF15, STAT4, POU2AF1, NFKB1, CLEC16A, IRF5, TNPO3, TYK2, IL7R, DENND1B, TNFRSF1A, SLC4A2, ABCB4, ALB, CD80, CXCL10, NFE2L2, TGFB1, LOXL2, IL12B, CXCL9, LOX, CXCR5, HIF1A, NOS3, KEAP1, SLC51A, ICAM3, MAPK14, CYGB, CDH5, SLC51B, IGFBP1, RELA, CCL5, UBD, ENTPD2, ABCG2, CD3D, NSA2, KRT7, IL4, PPARGC1A, HAMP, ACE, VEGFA, JAK2, SLCO1C1, MMP13, HMOX1, ACE2, DAG1, HHIP, CPEB1, MAS1, MAP3K14, MMP2, MMP3, PDE5A, MMP9, RPS6KB1, AGT, COL1A1, REN, CCN2, AQP4, HLA-DPB1, IL12RB2, IKZF3, HLA-DRA, IL16, GSDMB, IL21R, PRKCB, SYNGR1, ORMDL3, ZPBP2, TNFSF8, PAX3, DGKQ, MAPK8IP1P1, PLCL2, KANSL1-AS1, MAPK8IP1P2, PLCB1, RPL3, TP63, IL10, NSF, RAD51B, KANSL1, CD58, PSMG4, CYP21A2, ATXN2, LINC01100, LINC02820, LINC02210-CRHR1, SKIV2L, RPS6KA4, SP100, MAPT, MANBA, TSBP1-AS1, IL12A-AS1, ELMO1, LTBR, EIF4EP2, SH2B3, DLEU1, STAT1, MAPT-IT1, NAB1, TSBP1, DELEC1, MAPT-AS1, CCDC88B, ARHGAP31, PRICKLE1, GLI3, PSMD3, TMEM39A, LINC02210, SPPL2C, WNT3, SDK1, COL17A1, SLC22A23, SLC17A8, CNTN5, PRDM16, CTLA4, CDK12, GRIK1, HLA-DRB1, MED1, EIF4E, RBM45, ARID3A, TIMMDC1, STH, FBXL20, EXOC3L4, DLAT, RMI2, DDX6, TNF, VDR, IFNG, NUP210, PML, TLR4, FOXP3, CDKN1A, FGF19, IL17A, GPT, OGDH, IL1B, CD40LG, CXCL8, SQSTM1, CYP7A1, ABCB11, CDKN2A, HLA-DOA, PPARA, HK1, BCL2, DLST, PDC, ABCB1, TNFSF11, PDHX, TRIM21, NR1I2, ICAM1, SLPI, ATHS, MIR506, GGT1, CD14, SLC12A9, NAT10, HGF, GGTLC5P, HLA-DQA1, GGTLC3, GGT2, CD40, GGTLC4P, PDLIM3, CD19, PTPN22, IL2, ATRNL1, IL5, ASRGL1, ATN1, TBC1D9, MIR21, CCL27, DBT, ALPP, TGFBR2, XPR1, SULT2A1, SYCE1L, C4B_2, LOC102723407, LOC102724197, LOC102724971, TLR2, IL21, GPBAR1, SLC22A1, SLCO1B1, KHDRBS1, BTG3, NUP62, ABCC3, SOCS1, B3GAT1, DCTN4, GGTLC1, CDR3, NELFCD, KRT20, KLHL1, NR1H4, KLHL12, TP53, SLC10A2, H3P10, ESR2, LGALS3BP, HLA-A, CDKN1B, C4A, CYP3A4, C4B, CX3CR1, GTF2H1, POU2F1, MS4A1, CTSZ, GABPA, NRAS, CCR5, CD86, CXCR3, IL7, CD79A, FBL, ESR1, SLC10A1, HLA-DRB3, APOE, HNF4A, IL2RA, HSPD1, PPP1R2C, GLB1, GATM, PDCD1LG2, LRRC32, PNPLA3, MARCKSL1, FOXO3, FOXO1, WLS, FH, AGBL2, VTCN1, TNFAIP8L2, SLC25A1, POGLUT1, NR3C1, SIAE, IGF1, IFI27, SOST, TMED7, HMGB1, IL23A, HLA-DQB1, HLA-DPA1, HLA-B, TLR9, PDP1, COG6, RBFOX1, DPP8, GZMB, ITLN1, PRPF40A, WDR11, GSTM2, PRAM1, GSTM1, JPH3, JAM3, NQO1, NBPF3, MIR223, MIR505, CD1D, CD1C, DDR1, SPATA31A3, BRCA1, BHMT, BCR, BCL3, ATM, AREG, ABCC6, DEFB4B, FASLG, TMED7-TICAM2, FAS, APEX1, AIRE, ANXA11, ANXA2, ACTB, LINC02605, H3P23, MIR425, MIR210, DNMT1, CD28, DPP9, DNASE1, DMBT1, SP140L, TBX21, DBA2, DEFB4A, FCRL3, CTHRC1, DEFB1, LRG1, CYP2D6, COL9A3, CNGB1, CCR7, CHUK, CHRM3, CFTR, CD74, LINC01193, TICAM2, MIR155, MIR197, CD207, CD274, SCHIP1, POLR2G, SERPINA1, WNT2B, PRRC2A, PDK4, FOSL1, KMT2D, CDK2AP1, PDGFB, NR0B2, PDCD1, OPRM1, RNASET2, TNFRSF11B, DDR2, NOTCH1, TNFSF10, TNFSF9, TNFRSF11A, IL18R1, NFYA, MYD88, WASF1, ABCC1, HAP1, MIF, PIK3CA, VCAM1, EBAG9, UGT2B4, SOAT1, CXCL12, CCL24, SPINT1, SPP1, SRY, CCL20, CCL11, STAT3, SCTR, STAT5A, STAT5B, SERPINB3, TFF3, S100A12, RDX, TGM2, PTGS2, TLR3, PSMD9, PSMA4, PRF1, PPARG, TPMT, TNFSF4, CD99, MBL2, ICOS, TNFSF13B, ITGB2, ITGAV, RIPK3, ITGAL, PDZD2, ITGA5, ITGA1, ISG20, IL18, IL13, ICOSLG, SLC44A1, CLDN14, IL6, SS18L1, IL1RN, IL1A, INTU, AGO2, IL37, IGHG3, HPGDS, SLCO1B3, TRBV10-1, ABO, ITIH4, DCTN6, KLF4, KRT18, SLIT2, NTN1, SMAD3, HDAC9, KMT2B, SMAD2, CD180, LTA, LRP1, NR1I3, LPA, DGCR2, LORICRIN, EBI3, KLRG1, CALCOCO2, ABCC4, CCL26, LGALS3, CIB1, ZNRD2, LEP, GNLY, LAMP1, L1CAM, ABCA1

Drugs

(2S)-2-{[(2R)-2-[({[3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepin-8-yl]oxy}acetyl)amino]-2-(4-hydroxyphenyl)acetyl]amino}butanoic acid, Elafibranor, Engineered variant of recombinant human fibroblast growth factor 19 (FGF 19), Maralixibat, Obeticholic acid ( OCALIVA ), Seladelpar, Ursodeoxycholic acid ( DELURSAN, URSO, URSOLVAN ), Variant of recombinant human fibroblast growth factor 19

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Description

Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that usually affects middle-aged women and eventually leads to liver failure (summary by Kaplan, 1996).

For a discussion of genetic heterogeneity of primary biliary cirrhosis (PBC), see PBC1 (109720).

Mapping

To replicate the findings of Hirschfield et al. (2009) and to evaluate the relevance of identified loci to PBC susceptibility, Hirschfield et al. (2010) tested an additional independent cohort of 857 individuals with PBC and 3,198 controls, all of European descent, for PBC associations with 36 SNPs across 24 loci. The combination of these replication results and the prior genomewide association data yielded a genetic dataset derived from 1,351 PBC cases and 4,700 controls. The locus on chromosome 7q32 near the IRF5 (607218)-TNPO3 (610032) genes was confirmed by this analysis (SNP rs10488631, replication dataset p = 1.13 x 10(-8), OR = 1.58; combined dataset p = 8.66 x 10(-13), OR = 1.57). Fine mapping at this locus showed that the strongest signals were from rs12539741 and rs2070197 alleles. These variants map to just 3-prime of the IRF5 coding region and are in tight linkage disequilibrium with one another, and their associations with PBC reached fine-mapping p values of 1.65 x 10(-10) (odds ratio = 1.63) and 3.74 x 10(-10) (odds ratio = 1.62), respectively.

Liu et al. (2010) identified rs10488631 at chromosome 7q32 as a risk allele for primary biliary cirrhosis with an odds ratio of 1.63, p = 2.78 x 10(-10).