Cytokine gene polymorphisms and acute human liver graft rejection

Warlé, Michiel C.

doi:10.1053/jlts.2002.33967

Cited by 47 publications

(25 citation statements)

References 62 publications

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“…33 In liver transplant recipients, the TNF-a high genotype was associated with acute rejection in some studies [51][52][53] but not in others. [54][55][56] The TNF-a high genotype correlates with acute rejection in multiple adult kidney transplant studies from various demographic populations. 23,[45][46][47]57 Interleukin-6.…”

Section: Interleukinmentioning

confidence: 99%

Pharmacogenomics and lung transplantation: clinical implications

2006

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Section: Interleukinmentioning

confidence: 99%

Pharmacogenomics and lung transplantation: clinical implications

2006

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“…For example, the tumor necrosis factor (TNF)-A-308 polymorphism was found to be associated with severe rejection after heart, kidney, and liver transplantation'-4 and with a wide variety of diseases, such as primary sclerosing cholangitis,5,6 autoimmune hepatitis,GJ cerebral malaria,s mucocutaneous leishmaniasis,g and asthma.10 These associations were not always confirmed; for example, some studies could not show a relationship between the TNF-A-308 gene polymorphism and liver graft rejection. [11][12][13] The reasoning behind the proposed involvement of cytokine gene polymorphisms in diseases or disease manifestations is that they may influence in vivo cytokine levels. This presumption is based on the observation that individuals differ with respect to the level of cytokine production after in vitro culture of their cells and that these differences may be attributed partly to single-nucleotide or microsatellite polymorphisms of their cytokine genes.…”

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confidence: 99%

Are cytokine gene polymorphisms related to in vitro cytokine production profiles?

Warlé

2003

Liver Transplantation

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122

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Currently, there is much interest in the genetic basis for diseases or disease manifestations and, in particular, in whether they are related to cytokine gene polymorphisms. It has become accepted to denote such single‐nucleotide polymorphisms of cytokine genes by their presumed association with high or low in vitro cytokine production. In this article, we analyze the relationship between cytokine gene polymorphisms and in vitro tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin (IL)‐10 and IL‐13 production, both in liver transplant recipients and in healthy volunteers. The evaluated cytokine gene polymorphisms involved TNF‐A‐308; TNF‐d3; IFN‐G+874; IL‐10‐1082, ‐819, and ‐592; and IL‐13+2043, and ‐1055. For healthy volunteers, we observed a relationship between polymorphisms of TNF‐d3 and IL‐10‐1082 with in vitro production of TNFα and IL‐10, respectively, whereas no significant associations were found for the other tested cytokine gene polymorphisms. For liver transplant recipients, no significant relationship could be established between any of the cytokine gene polymorphisms and in vitro production of corresponding cytokines. Also, we reviewed the literature for the association between cytokine gene polymorphisms and in vitro cytokine production in various patient groups and healthy volunteers. We found that the cellular sources, from which the cytokines were released into the culture supernatant, were different between studies. They were either whole blood, isolated monocytes, or peripheral blood mononuclear cells (PBMC). Also, the in vitro incubation protocol varied to a great extent between studies. This applied for the used in vitro stimulant, the concentration of a particular stimulant, and the length of the incubation period. Moreover, the study populations were either healthy individuals or very diverse patient groups. Therefore, it was impossible to evaluate whether in vitro cytokine production profiles really can be deduced from a particular cytokine gene polymorphism. Given the inconclusive findings, we propose to set up a multicenter workshop in which the relationship between certain cytokine gene polymorphisms and in vitro cytokine production is analyzed, using an identical in vitro cell culture system and study population. Furthermore, we suggest that cytokine gene polymorphisms be described by their localization within the gene or gene‐promoter, rather than by their presumed in vitro cytokine production profile, to properly evaluate the relationship between cytokine gene polymorphisms and disease manifestations.

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“…This study investigated whether a genetic predisposition involving polymorphisms of TH1-, TH2-, or regulatory-type cytokine genes was associated with rejection following human liver transplantation. Several polymorphisms in cytokine genes have been investigated for their possible relationship with cytokine production (Platz et al, 1996;Warlé et al, 2002;Shi et al, 2008;Liu et al, 2009;Zhang and Sun, 2010;Rattanasiri et al, 2013) and graft rejection. Polymorphisms of IL10, TNF, and TGFB1 have been reported to be closely linked to AR (Bathgate et al, 2000;Jonsson et al, 2001;Mas et al, 2004;Azarpira et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Although some studies have shown an effect on rejection (Warlé et al, 2002;Rattanasiri et al, 2013), others have shown no association (Conti et al, 1998;Xie et al, 2008). The regulatory-type cytokines, such as transforming growth factor-b1 (TGF-b1), may influence both TH1-and TH2-type cytokines in the immune response (Liu et al, 2009), and some researchers have reported that they are upregulated in rejection (Eikmans et al, 2002), while others have reported no relationship (Eurich et al, 2011;Rattanasiri et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Relationship between cytokine gene polymorphisms and acute rejection following liver transplantation

Rj²,

Wang

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Acute rejection (AR) recurrence after liver transplantation (LT) is one of the major complications that leads to chronic graft dysfunction. It has been reported that the polymorphisms in some cytokine genes are associated with human liver allograft rejection. This study mainly investigated the associations between polymorphisms in the genes encoding interleukin-10 (IL10), transforming growth factor-b1 (TGFB1), and tumor necrosis factor-a (TNF), and the risk of AR recurrence. We enrolled 359 LT recipients; they were divided into two groups: an AR group (N = 165) and a non-AR group (N = 194) according to whether they experienced rejection within the first month following liver transplantation. After providing informed consent, blood was collected and DNA was extracted. The single nucleotide polymorphisms of IL10 (-1082, -819, and -592), TGFB1 (+869 and +915), and TNF (-308) were investigated according to the methods used in previous studies. A significant difference was observed in the distribution of allelic frequencies at position +869 in TGFB1 between the AR and non-AR groups (P = 0.000). However, no significant differences (P > 0.05) were found in the genotype distributions in IL10, TNF, and TGFB1 between the AR and non-AR groups. Our study suggests that the +869 gene polymorphism of TGFB1 is significantly associated with liver graft rejection, while the other gene polymorphisms investigated in IL10, TNF, and TGFB1 are probably not risk factors for AR in LT recipients.

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Cytokine gene polymorphisms and acute human liver graft rejection

Cited by 47 publications

References 62 publications

Pharmacogenomics and lung transplantation: clinical implications

Pharmacogenomics and lung transplantation: clinical implications

Are cytokine gene polymorphisms related to in vitro cytokine production profiles?

Relationship between cytokine gene polymorphisms and acute rejection following liver transplantation

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