Primary Biliary Cirrhosis Associated withHLA, IL12A,andIL12RB2Variants

Abstract

BACKGROUND-Primary biliary cirrhosis is a chronic granulomatous cholangitis, characteristically associated with antimitochondrial antibodies. Twin and family aggregation data suggest that there is a significant genetic predisposition to primary biliary cirrhosis, but the susceptibility loci are unknown.

Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

“…129 PBC is an autoimmune disease characterized by the slow progressive destruction of the small bile ducts within the liver. 133 In 2006, Milkiewicz et al 130 reported that PTPN22 was not associated with PBC in Canada. This result was confirmed by a GWAS in 2009 with samples from both the USA and Canada.…”

Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients

“…In this regard, other non-HLA genes are being considered to contribute to disease development [9,10].…”

“…In addition to CTLA4 polymorphisms, HLA class II, IL12A, IL12RB, and several other candidate SNPs were disclosed as predisposition genes for PBC by a high-density genome-wide association study [9]. Since these SNPs have not been extensively examined in a large Japanese population, the present study sought to evaluate the involvement of CTLA4 SNPs and haplotype SNPs in susceptibility to PBC and disease progression in Japanese patients.…”

the Utility of Genome-Wide Association Studies in Hepatology

“…The orange area illustrates what types of genetic variants that are detectable using 10,000 cases and 10,000 controls with the significance level set at 10 À6 . In practice, GWAS target risk variants with odds ratios > 1.1, an allele frequency !5%; variants in the lower range of what is detectable only exert a small impact on the relative sibling risk (e.g., 1.005-1.01 of a total of [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Study designs other than GWAS will be required to detect very rare and/or very weak effects outside the orange area.…”

“…Among the GWAS publications, only 12 are concerned with hepatological conditions (gallstone disease, levels of hepatic biochemistries, nonalcoholic fatty liver disease [NAFLD], primary biliary cirrhosis [PBC], primary sclerosing cholangitis [PSC], flucloxacillin-induced liver injury, and chronic hepatitis B and chronic hepatitis C treatment outcome). [3][4][5][6][7][8][9][10][11][12][13][14] Applied correctly, there is definitely potential for this tool to be useful in hepatology, as exemplified by the discoveries already made.…”