Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Susceptibility to autoimmune hepatitis is associated with the HLA-DR3 and DR4 haplotypes, but which genes are directly involved in the pathogenesis, has not been established. Low levels of complement component C4 and elevated frequencies of C4 null allotypes have been described in patients, suggesting that the C4 genes, which are closely linked with the HLA loci, may play a role. We therefore examined restriction fragment length polymorphisms in the C4 and 21-hydroxylase genes, and determined HLA-A and B phenotypes, and HLA-DR, DQ and DP genotypes in a large series of Caucasoid patients with autoimmune hepatitis and matched controls. A DNA deletion of the C4A gene and the 21-hydroxylase A pseudogene was found to be present in 50% of patients compared to 23% of controls (Pc < 0.005, relative risk = 3.3). This increase, however, appears to be due to linkage disequilibrium with HLA-DR52a which was most strongly associated with the disease. Complete C4A deficiency, determined by homozygosity for the deletion increased the risk to 18.1 (16% versus 1%, Pc < 0.005), suggesting an additional role for C4 in disease susceptibility. C4 deletions were associated with an increased mortality and tendency to relapse whilst on treatment but did not correlate with age of onset of disease. Our data suggest that MHC-encoded susceptibility to autoimmune hepatitis is polygenic, involving the HLA-DR genes plus other loci, and C4 deficiency may be a marker of disease susceptibility and/or severity.
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PMID:Polymorphism in the human complement C4 genes and genetic susceptibility to autoimmune hepatitis. 785 9

Autoimmune hepatitis is an inflammatory liver disease in which the immune system is believed to orchestrate an immune attack onto the liver cell. Current knowledge suggests that both T helper 1 (TH1) and TH2 programmes are involved in the generation of the liver damage. Release of TH2 cytokines leads to the production of autoantibodies to the hepatocyte membrane that recruit killer cells. TH1 cytokines induce macrophage activation which contributes to hepatocyte destruction. Patients commonly possess the "autoimmune" HLA A1/B8/DR3 haplotype and a silent gene at the C4A locus with consequent partial deficiency of the complement component C4. Two main types of autoimmune hepatitis are recognised according to the presence of circulating non-organ specific autoantibodies. Patients with smooth muscle antibody and/or antinuclear antibody may be adults or children, while patients with antiliver kidney microsomal type 1 (LKM1) antibody are usually children or very young adults. In both types there is a preponderance of females. LKM1 antibody is also present in a proportion of adult patients, mainly male, with chronic hepatitis C virus infection. This observation originally led to the suggestion that hepatitis C virus may be the cause of this form of autoimmune hepatitis, but several studies have shown that the epitopes target of the LKM1 antibody in autoimmune hepatitis and chronic hepatitis C virus infection differ. Although autoimmune hepatitis responds satisfactorily to immunosuppression in the short term, progression to cirrhosis is frequent. It is hoped that ongoing research will provide a better understanding of the pathogenic mechanisms of liver damage leading to a more effective and specific mode of treatment.
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PMID:Autoimmune hepatitis. 897 37