A study of cytokine gene polymorphisms and protein secretion in renal transplantation

Cartwright, Nicola; Keen, Leigh; Demaine, Andrew; Hurlock, N.J; McGonigle, R; Rowe, P. A.; Shaw, J; Szydlo, Richard; Kaminski, É.

doi:10.1016/s0966-3274(01)00026-0

Cited by 50 publications

(29 citation statements)

References 36 publications

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“…With the aid of 73 transplant centers who provided cell samples and information on transplants, we were able to analyze the influence of TGFb1, TNFa, IL4Ra, and IL10 polymorphisms on kidney graft survival in more than 4000 Caucasian transplant patients. Perhaps the most interesting finding of this study is that none of the four investigated cytokine polymorphisms was associated with the outcome of primary kidney transplants; a result that differs from results obtained in smaller series [5][6][7]9,10,[30][31][32]. We were only able to demonstrate a statistically significant effect of the TNFa high-responder genotype on graft survival in retransplant patients.…”

Section: Discussioncontrasting

confidence: 90%

Relevance of IL10, TGFβ1, TNFα, and IL4Rα Gene Polymorphisms in Kidney Transplantation: A Collaborative Transplant Study Report

Mytilineos¹,

Laux

Opelz

2004

American Journal of Transplantation

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Single nucleotide polymorphisms (SNPs) of cytokine genes have been shown to influence cytokine plasma levels. Cytokines are important mediators during organ graft rejection. It was reported that certain cytokine genotypes are associated with improved kidney graft survival. In the present study, SNPs within the IL10 promoter gene, the first exon of the TGFb1 gene, the TNFa promoter gene, and the IL4Ra gene were analyzed in 2298 first and 1901 repeat cadaver kidney recipients. We found no significant effect on the survival rate of first grafts. Among retransplants, we observed that recipients who were homozygous for the high TNFa producer genotype −308 A had a significantly lower graft survival rate than patients who were carriers of the low producer genotype −308 G (at 3 years: 63.0% vs. 79.5%; p corrected = 0.0116). The results of this large-scale study suggest that IL10, TGFb1, TNFa , and IL4Ra cytokine genotypes do not affect the survival of primary kidney grafts. The outcome of retransplants appears to be affected by TNFa genotypes only.

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Section: Discussioncontrasting

confidence: 90%

Relevance of IL10, TGFβ1, TNFα, and IL4Rα Gene Polymorphisms in Kidney Transplantation: A Collaborative Transplant Study Report

Mytilineos¹,

Laux

Opelz

2004

American Journal of Transplantation

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“…The heterogeneity of the observed association between in vitro IFNy production and the IFN-G+ 874 polymorphism may be attributable to the fact that different patient populations were tested: liver transplant recipients in our study, pediatric renal transplant recipients,22 and adult renal transplant recipients. 37 Also, in our study and the above-mentioned studies, different in vitro stimulation protocols were used: respectively, ConA (in our study), PHA/LPS,22 and a completely different in vitro allostimulation culture system. 37 Previously published studies in which associations were investigated between in vitro IL-10 production and IL-10-1082 gene polymorphism are shown in Table 4.…”

Section: Discussionmentioning

confidence: 99%

“…37 Also, in our study and the above-mentioned studies, different in vitro stimulation protocols were used: respectively, ConA (in our study), PHA/LPS,22 and a completely different in vitro allostimulation culture system. 37 Previously published studies in which associations were investigated between in vitro IL-10 production and IL-10-1082 gene polymorphism are shown in Table 4.…”

Section: Discussionmentioning

confidence: 99%

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

Warlé

2003

Liver Transplantation

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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“…28 Studies on the impact of recipient À174 G/C polymorphism on acute rejection following renal transplantation have provided conflicting results. One study found a lower frequency of G/G or G/C genotype in recipients who developed acute rejection, 29 while another found a higher frequency of these genotypes, 30,31 although the results of these studies were not statistically significant. High levels of the G/G and G/C IL-6 promoter genotypes have been shown to be significantly associated with decreased risk of acute rejection following liver transplant.…”

Section: Discussionmentioning

confidence: 84%

Recipient IL-6-572C/G genotype is associated with reduced incidence of acute rejection following liver transplantation

Yao

Feng

et al. 2013

J Int Med Res

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Objective: Acute rejection resulting from alloimmune responses is a major risk factor affecting patient survival following liver transplantation. Since interleukin (IL)-6 can mediate acute rejection, the association between IL-6 gene single nucleotide polymorphisms (SNPs) and incidence of acute rejection in liver transplant recipients was investigated. Methods: Patients who received liver transplant between January 2005 and December 2010 were typed for IL6-572C/G (rs1800796) polymorphisms using the snapshot technique. Association between genotype and acute rejection was analysed using the SNP Statistics website: http:// bioinfo.iconcologia.net/snpstats/start.htm. Allelic and genotypic distributions for rs1800796 were compared among 335 patients with or without acute rejection within the first 6 months following liver transplant. Results: Incidence of acute rejection was 11.94%. A heterozygous CG genotype for IL6-572C/G was associated with a lower acute rejection rate compared with homozygous CC or GG genotypes. Conclusion: IL6-572 CG genotype may be related to protection from acute rejection following liver transplant in Han Chinese patients.

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A study of cytokine gene polymorphisms and protein secretion in renal transplantation

Cited by 50 publications

References 36 publications

Relevance of IL10, TGFβ1, TNFα, and IL4Rα Gene Polymorphisms in Kidney Transplantation: A Collaborative Transplant Study Report

Relevance of IL10, TGFβ1, TNFα, and IL4Rα Gene Polymorphisms in Kidney Transplantation: A Collaborative Transplant Study Report

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

Recipient IL-6-572C/G genotype is associated with reduced incidence of acute rejection following liver transplantation

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