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)

Fifty-one patients with autoimmune hepatitis have been studied for HLA association by conventional serology and also by modified polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping. HLA-DR4 was significantly associated with autoimmune hepatitis (46 of 51 patients, 90.2%). DNA typing of the DRB1 gene for 43 DR4-positive patients by using the PCR-RFLP technique revealed that of 43 patients, 33 had DRB1*0405 (Dw15), five had DRB1*0406 (DwKT2), four had DRB1*0403 (Dw13a), two had DRB1*0401 (Dw4), two of 43 had DRB1*0407 (Dw13b) and one had DRB1*0408 (Dw14b). Thus, there was no significant difference in Dw frequencies between DR4-positive patients and DR4-positive healthy subjects. These findings suggest that the DR4-specific sequence (Val 11 and His 13 at amino acid positions 11 and 13, respectively), but not particular Dw-associated DR4 sequence, in the first domain of the DRB1 chain contributes to susceptibility to autoimmune hepatitis among Japanese. Interestingly, all five of the DR4-negative patients had the DR2 specificity (DRB1*1502 or 1601). Taken together, these results imply that the basic amino acids at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), are most important for determining the predisposition to autoimmune hepatitis.
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PMID:A possible association between basic amino acids of position 13 of DRB1 chains and autoimmune hepatitis. 135 Feb 67

The frequencies of HLA B54, DR4, DR53 and DQ4 were significantly higher in patients with autoimmune hepatitis than in healthy controls. HLA-DR4 was most frequently associated with autoimmune hepatitis. To define the HLA class II gene which has the susceptibility or resistance to autoimmune hepatitis, we performed HLA class II genotyping using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. The frequency of DRB1*0405 was significantly higher in autoimmune hepatitis than in controls. However, there was no significant difference in the frequency of the DR4 associated Dw-allele between the patients and the controls who were DR4-positive. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-associated Dw-alleles compared with the DR2-positive controls. Comparison of the amino acid residues of DRB1 chain suggested that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among Japanese.
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PMID:[Molecular biological analysis of HLA class II gene in autoimmune hepatitis among Japanese]. 809 52

In hepatitis C, both susceptibility to infection and the course of disease may depend on differences in the immune response. As the major histocompatibility complex (MHC) plays a crucial role in antigen presentation, we investigated a possible relationship between susceptibility to hepatitis C virus (HCV) infection and human leucocyte antigen (HLA) alleles. Therefore, phenotype frequencies of HLA were compared in 186 anti-HCV positive patients with end-stage renal disease (ESRD) to 328 anti-HCV negative patients with ESRD. HLA class I alleles were determined serologically and HLA class II alleles (DRB1, DQA1, DQB1) by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) technique. Additionally, in anti-HCV positive patients we looked for a relationship between the activity of hepatitis C (indicated by elevation of transaminases or the presence of viremia) and HLA determinants. For the three criteria (antibody status, elevation of transaminases and viremia) a significant association to HLA alleles was not found in patients with ESRD. This suggests that neither susceptibility to HCV infection nor the biochemical activity of hepatitis and HCV-RNA positivity seem to be strongly related to HLA status in Caucasian patients with end-stage renal disease.
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PMID:No significant influence of HLA determinants on susceptibility to hepatitis C virus infection in Caucasian patients with end-stage renal disease. 902 18

Susceptibility to autoimmune hepatitis (AIH) is associated with the HLA A1-B8-DR3 haplotype, DR4 antigen, and, more specifically, the HLA DRB3*0101, DRB1*0301, and DRB1*0401 alleles. Few investigators, however, have examined the HLA C locus in AIH, which warrants detailed study in view of its recently described roles in immunoregulation. Eighty-seven adult, white patients with well-characterized type 1 AIH and 100 controls were studied. HLA C and HLA DRB1 alleles were assigned by polymerase chain reaction (PCR)-based genotyping. HLA A and B antigens were determined by standard microlymphocytotoxicity assay. Extended haplotypes were constructed according to known patterns of linkage disequilibrium. Only one HLA C locus allele, Cw*0701, which was present in 54% of patients versus 34% of controls (P = .006; relative risk [RR] = 1.54) was associated with AIH. The overall increase in the frequency of the Cw*07 gene (70.1% of patients vs. 54% of controls; P = .024; RR = 1.3) was due entirely to inheritance of the Cw*0701 allele rather than the other Cw*07 alleles, Cw*0702, *0703, and *0704. The RR for Cw*0701 (RR = 1.54) is greater than that for HLA A1 (RR = 1.33) and DRB1*0301 (RR = 1.49), but less than that for HLA-B8 (RR = 1.75). The present findings suggest that the gene or genes conferring susceptibility to AIH lie in the region centromeric to the HLA A locus between HLA C and DRB1. Although linkage disequilibrium with both B8 and DRB1*0301 may account for our finding of an increased frequency of Cw*0701, it is also possible that this allele contributes to disease susceptibility, perhaps by interaction with natural killer cells or cytotoxic T lymphocytes.
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PMID:HLA-C genes and susceptibility to type 1 autoimmune hepatitis. 932 30

The human leukocyte antigen is a crucial genetic factor that initiates or regulates immune response by presenting foreign or self antigens to T lymphocytes. The aim of this study was to investigate whether HLA polymorphism is associated with the onset or progression of liver injury in chronic hepatitis C virus (HCV) infection. We determined HLA class I antigens and class II alleles in 130 hepatitis C virus (HCV)-infected patients (33 carriers with persistently normal alanine transaminase [ALT] values and 97 patients with chronic liver disease [CLD]). HLA class I (A, B) was typed serologically, and class II (DRB1, DQB1) was typed by means of polymerase chain reaction-restriction fragment length polymorphism methods. The frequencies of DRB1*0405 and DQB1*0401 were higher in HCV-infected patients than in uninfected subjects. Among HCV-infected patients, the frequencies of B54, DRB1*0405, and DQB1*0401 were significantly higher in patients with CLD than in those carriers with persistently normal ALT values, whereas DRB1*1302, DRB1*1101, and DQB1*0604 were more frequently found in carriers with persistently normal ALT values than in patients with CLD. From extended haplotype analyses, in carriers with B54-DRB1*0405-DQB1*0401 haplotype, the risk of having liver injury was 13.2 times greater than in carriers with DRB1*0405-DQB1*0401 but without B54 [P = 0.0015, Haldane odds ratio = 13.2 (95% confidence interval, 1.7-103.8)]. In contrast, carriers with B44-DRB1*1302-DQB1*0604 had a 12.7-fold lower relative risk of developing liver injury compared to those with the haplotype containing B44 but not DRB1*1302-DQB1*0604 [P = 0.0076, Haldane odds ratio = 0.079 (0.009-0.695)]. Our findings show that extended haplotypes including class I B54 are closely associated with the progression of liver injury, whereas extended haplotypes including class II DRB1*1302-DQB1*0604 are associated with low hepatitis activity in chronic HCV infection.
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PMID:Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus. 942 43

Both direct viral cytopathic effects and host immune responses appear to be important in the pathogenesis of hepatitis C virus (HCV) infection. Liver transplantation provides a means to explore the role of the immune system in the development of HCV-related liver damage through comparing the natural history of HCV in patients with different degrees of donor-recipient human leukocyte antigen (HLA) matching. We evaluated 36 patients with recurrent hepatitis C viremia following liver transplantation to determine whether hepatocellular injury or progression to bridging fibrosis occur more rapidly when donor and recipients share HLA alleles. HLA typing for the HLA-A and HLA-B loci was performed by serological techniques and PCR-based oligotyping was used to type alleles of the DRB1, DRB3, DQA1, and DQB1 loci. A median of eight liver biopsies, obtained during a median follow-up of 36 months, were reviewed per patient. Donor-recipient sharing of alleles of HLA-DQB1 or DRB1 was associated with more rapid development of recurrent hepatitis by univariate analysis (chi2=5.7, P=0.02 and chi2=5.54, P=0.02 respectively). However, only sharing of HLA-DRB1 alleles was identified as an independent predictor of reduced time to recurrent histologic injury by multivariate analysis (chi2 =5.74, P=0.02). Furthermore, sharing of HLA-DRB3 and histologic evidence of rejection were associated with more rapid progression to bridging fibrosis both by univariate methods (chi2=4.12, P=0.04 and chi2=4.66, P=0.03 respectively), and by multivariate analysis (chi2=13.01, P=0.001). These findings suggest that HLA class II-restricted immune responses may contribute to the pathogenesis of HCV-related liver injury in liver transplant recipients.
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PMID:Donor-recipient sharing of HLA class II alleles predicts earlier recurrence and accelerated progression of hepatitis C following liver transplantation. 986 33

Hepatitis C outcome is likely related both to viral factors and host's immune responses. We correlated the severity of liver disease with human leukocyte antigen (HLA) genes (C4A, C4B, TNFA, TNFB, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, TAP1, and TAP2) in three groups of subjects: 99 patients with chronic hepatitis, 41 asymptomatic carriers, and 179 uninfected controls. Patients with grade/stage 3 to 4 hepatitis significantly differentiated for their low frequency of alleles TNFB*1, DRB1*1104, and DRB3*03, which had a protective role, and high frequency of allele DRB1*1001, which was associated with disease severity. HLA-DRB*11 subtypes were differentially distributed: DRB1*1104 was most frequent in carriers, whereas DRB1*1101 was more frequent in patients. The TAP1C,2A haplotype was also underrepresented in patients with respect to controls. Finally, a decrease of heterozygous subjects was observed in patients with respect to carriers at the DQB1 locus. Multivariate analysis by correspondence analysis and multiple logistic regression indicated that age, sex, and hepatitis C virus (HCV) type were the strongest risk factors; however, some immunogenetic variables (TNFB*1, DRB1*1104, and DRB3*03) showed an independent contribution, especially in comparing patients with extreme manifestations of disease. The involvement of different genes in various HLA subregions suggests that anti-HCV responses are modulated by a complex gene interplay rather than by single alleles.
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PMID:Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease. 1009 75

Genetic susceptibility to type 1 autoimmune hepatitis in white northern Europeans is related to female sex, HLA alleles encoding the six amino acid sequence LLEQKR at positions 67-72 of the DRB1 polypeptide, and CTLA-4 gene polymorphism. The principal HLA alleles associated with type 1 autoimmune hepatitis in Britain and North America are DRB1*0301 and DRB1*0401. In this model of susceptibility, lysine at position 71 of the expressed DR molecule is the critical amino acid. In Japan, Argentina and Mexico, susceptibility is linked to DRB1*0405 and DRB1*0404. These two alleles encode arginine at position 71 rather than lysine, but they share the motif LLEQ-R with DRB1*0401 and DRB1*0301. Thus, K or R at position 71 in the context of LLEQ-R may be critical for susceptibility. This "shared motif" or "epitope" may optimize T-cell recognition of autoantigen, and other alleles that encode lysine at DRbeta71 may also affect susceptibility and outcome, possibly by increasing the density of lysine or arginine 71 molecules on the surface of antigen-presenting cells. Since the DRB1*0301 allele is part of the extended ancestral 8.1 haplotype, it carries with it additional risk factors for autoimmunity, including TNFA*2 and C4A*Q0. Type 1 autoimmune hepatitis is a polygenic disorder and other yet undefined polymorphic genes may be non-specific immunoregulators. These additional MHC encoded genes and other non-MHC encoded genes may be important determinants of disease susceptibility and severity in type 1 autoimmune hepatitis.
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PMID:Genetic susceptibilities for immune expression and liver cell injury in autoimmune hepatitis. 1080 21

Susceptibility to autoimmune hepatitis type I (AIH-1) has been associated with HLA-DR3, DR52, and DR4 antigens in Caucasian and Oriental patients. However, in Brazil, disease susceptibility is primarily linked to DR13 and DR52. In this highly admixed population, we find different DR13-associated haplotypes, presenting a unique opportunity to discriminate relevant genes within a tightly linked genomic region. To identify the primary susceptibility locus, we sequenced DR13 alleles of 39 patients with AIH-1 and 22 controls. Patients were almost exclusively DRB1*1301, but half of controls typed DRB1*1302. HLA-DQ haplotypes were varied. Oligotyping of DRB3 locus of all patients and also within the HLA-DR13 positive group showed an allele distribution comparable to controls, confirming that the stronger association lies in the DRB1 locus. On the other hand, if DRB1*1301 is the major susceptibility factor in our sample, the only amino acid different from DRB1*1302 in position 86, corresponding to pocket 1 in the peptide-presenting groove, may be important. We propose that peptide presentation leading to pathogenesis of AIH-1 may be quite stringent, but will also be affected by other strong genetic or environmental susceptibility factors, which would explain the various HLA molecules associated to the disease in the different populations.
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PMID:Analysis of HLA haplotypes in autoimmune hepatitis type 1: identifying the major susceptibility locus. 1118 27

Current hypotheses suggest that autoimmune hepatitis (AIH) is triggered by an environmental factor in a genetically susceptible host. Multiple genes may interact to produce a "permissive gene pool" that determines both disease risk and phenotype. Studies of type 1 AIH have focused on the major histocompatibility complex (MHC), mapping susceptibility to the DRB1 region. Three different molecular models have been proposed based on histidine at DRbeta13, lysine at DRbeta71, and valine at DRbeta86. Although the lysine-71 model has been adapted to explain data from several other studies, the DRbeta13 and DRbeta86 models are exclusive to their founder populations. It is possible that all three models apply and that the different associations reflect the "molecular footprint" of the common environmental triggers in the different study populations. Studies outside the MHC have identified the CTLA4 A+49G, G allele as a possible second risk allele. There are many neutral polymorphisms in the genome, and further studies are currently needed to identify other disease alleles in type 1 AIH.
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PMID:Genetics in autoimmune hepatitis. 1244 7


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