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)

Possible associations between particular human leucocyte antigen molecules and immunoallergic hepatitis have been suggested previously (HLA-A11 in halothane hepatitis, HLA-DR6 and DR2 in nitrofurantoin hepatitis, HLA-B8 in clometacin hepatitis). In this study the HLA haplotype was determined in 71 patients with idiosyncratic hepatitis due to different drugs. The prevalence of HLA-A11 was twice as high in the 71 patients in the study (23%) as in controls (12%), but p-values were not significant when corrections were made for the large number of comparisons (n = 39). The prevalences of HLA-DR2, DR6, and B8 were similar in the 71 patients and in controls. When hepatitis due to particular drugs was considered, HLA-A11 was found to be present in six of 12 patients (50%) with hepatitis caused by tricyclic antidepressants, and three of four patients (75%) with diclofenac hepatitis, compared to 12% in controls. HLA-DR6 was present in four of five patients (80%) with chlorpromazine hepatitis, compared to 22% in controls. In conclusion, the HLA phenotype does not contribute significantly to idiosyncratic drug-induced hepatitis considered collectively. Possible associations between some HLA molecules and the hepatotoxicity of certain drugs require further confirmation.
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PMID:Possible role of HLA in hepatotoxicity. An exploratory study in 71 patients with drug-induced idiosyncratic hepatitis. 801 43

The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] = 16.3, Pc < 10(-24)) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA-DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II beta chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] = 76%). In contrast to the class II associations in children, AAH was associated with HLA-DRB1*0405 (RR = 10.4, Pc <.005) but not with HLA-DRB1*1301 or HLA-DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] = 104.9, Pc < 10(-4)). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P =.003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors.
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PMID:Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition. 1057 14