the interleukin-1 and interleukin-10 gene polymorphisms in primary sclerosing cholangitis: no associations with disease susceptibility/resistance

Donaldson, Peter; Norris, Suzanne; Constantini, Patrizia K.; Bernal, W.; Harrison, Phillip; Williams, Roger

doi:10.1016/s0168-8278(00)80091-4

Cited by 30 publications

(4 citation statements)

References 35 publications

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“…They did not take into account other SNPs and did not consider either IL1A or the two IL-1 receptor genes. Similar studies in PSC have also drawn a blank 81 and, although there are also no IL10 associations in PBC, 82 preliminary data indicate strong links with the IL1 gene cluster. 9 Currently, there are many more cytokines to investigate in type 1 AIH, and studies are in progress to assess the role of IL-4, the CC-chemokine receptor-5 (CCR5), and IL-2, among others.…”

Section: Genetics Of Type 1 Aih Looking Beyond the Mhcmentioning

confidence: 72%

Genetics in Autoimmune Hepatitis

Donaldson¹

2002

Semin Liver Dis

112

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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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Section: Genetics Of Type 1 Aih Looking Beyond the Mhcmentioning

confidence: 72%

Genetics in Autoimmune Hepatitis

Donaldson¹

2002

Semin Liver Dis

112

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“…IL-10 genotype distribution was in a similar range as observed in 78 healthy health care workers in the UK, even though there was a slightly lower percentage of the heterozygous genotype (45%) and a slightly higher percentage of the homozygous IL-10 G/G genotype (27%) in this control group. 50 The distribution of the IL-10 genotype in prednisone good responders and prednisone poor responders is shown in Table 5. There was an overall protective effect from poor prednisone response in patients showing the IL-10 G/G genotype compared to the reference category (OR = 0.32, 95% CI = 0.10-0.99, P = 0.049), whereas we found no association of IL-10 genotype and risk of relapse in childhood ALL (OR = 1.10, 95% CI = 0.43-2.81, P = 0.837, Table 6).…”

Section: 2% (Il-10g*)mentioning

confidence: 99%

“…Subgroup analysis for IL-10 was performed and included haplotype and immunophenotype. Interestingly, the association of IL-10 50 for example, did not find a correlation between genotype and disease susceptibility nor resistance in primary sclerosing cholangitis, whereas Tagore et al 35 showed that there was a protective effect of high IL-10 levels against inflammatory bowel diseases. Edwards-Smith et al, 33 on the other hand, reported that high IL-10 levels predicted a poor treatment outcome using interferon-␣ for treatment of hepatitis C. Following solid organ transplantation, IL-10 and TNF have been shown to be associated with acute rejections and steroid resistance.…”

Section: 2% (Il-10g*)mentioning

confidence: 99%

Association of initial response to prednisone treatment in childhood acute lymphoblastic leukaemia and polymorphisms within the tumour necrosis factor and the interleukin-10 genes

et al. 2002

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Plasma levels of TNF and IL-10 have been associated with therapy outcome in haematological malignancies and are influenced by genetic variation due to germline polymorphisms within the TNF and IL-10 genes. Different TNF and IL-10 genetic polymorphisms might therefore also correlate with clinical outcome in childhood acute lymphoblastic leukaemia (ALL). We analysed the association of TNF and IL-10 polymorphisms with response to initial treatment and risk of relapse in 135 children with ALL, treated according to Berlin-Frankfurt-Mü nster (BFM) protocols. Our data showed a protective effect from prednisone poor response in patients with the IL-10 G/G genotype, whereas no association of the risk of relapse and IL-10 genotype was found. In the total study group, subjects expressing the TNF2 allele neither showed a statistically significant general association with prednisone response nor with risk of relapse compared to subjects homozygous for the TNF1 allele. Nevertheless, we did find a higher risk of relapse in poor prednisone responders expressing the TNF2 allele compared to poor prednisone responders not expressing the TNF2 allele. We conclude that IL-10 genotype might influence prednisone response in patients with childhood ALL, whereas TNF genotype seems to influence the risk of relapse in high risk ALL patients.

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“…It appears unlikely that susceptibility to PSC will prove to be attributable to a single gene locus, but will be acquired by inheriting one of a number of patterns of genetic polymorphisms, which together cause a predisposition to the development of the disease. Four key HLA haplotypes have been shown to be associated with the development of the PSC and some non‐HLA loci are being explored including CTLA‐4, CCR‐5, interleukin (IL)‐1, IL‐10 and MMP‐3 14, 15, 17–23 …”

Section: Pathogenesis Of Pscmentioning

confidence: 99%

Review article: current management of primary sclerosing cholangitis

Cullen

Chapman

2005

Aliment Pharmacol Ther

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Summary The management of primary sclerosing cholangitis (PSC) is hindered by incomplete understanding of the pathogenesis of the disease and the lack of good prognostic models. Few large randomized controlled trials of drug therapy have been published. Best practice in the management of PSC is currently based therefore on careful interpretation of the available evidence, close observation of individual patients and clinical experience of the disease. Drug therapy is useful for alleviating symptoms. Ursodeoxycholic acid may slow progression of the disease and reduce the frequency of complications. Consensus is emerging on the issues of screening for the malignant complications of PSC and the indications for liver transplantation are becoming broader and encompassing the earliest stages of cholangiocarcinoma. In view of the rarity of the disease in the general population, large international collaborations to study PSC are necessary to provide clearer answers in areas of uncertainty, and these are now beginning to emerge.

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the interleukin-1 and interleukin-10 gene polymorphisms in primary sclerosing cholangitis: no associations with disease susceptibility/resistance

Cited by 30 publications

References 35 publications

Genetics in Autoimmune Hepatitis

Genetics in Autoimmune Hepatitis

Association of initial response to prednisone treatment in childhood acute lymphoblastic leukaemia and polymorphisms within the tumour necrosis factor and the interleukin-10 genes

Review article: current management of primary sclerosing cholangitis

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