Cytokine Gene Polymorphism and Heart Transplant Rejection1

Turner, David M.; Grant, S. C. D.; Yonan, Nizar; Sheldon, Stephen H.; Dyer, Philip A.; Sinnott, Paul J.; Hutchinson, Ian V.

doi:10.1097/00007890-199709150-00021

Cited by 224 publications

(126 citation statements)

References 8 publications

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“…TNF-a acts as a pro-inflammatory cytokine and has been implicated in both acute and chronic rejection in several organ allograft populations (10). Despite this strong association, we observed no significant differences in the distribution of TNFa genotypes between ethnic populations.…”

Section: Discussioncontrasting

confidence: 58%

“…We did observe, however, a difference in the allelic distribution of the TNF-a (A) allele in patients (p Ω 0.042) compared with healthy controls (Figure 2). Expression of this allele is associated with a six-to sevenfold increase in TNF-a transcription in vitro and a higher susceptibility for allograft failure (2,3,10). We also noted a significant association between the IL-2 polymorphic (G) allele and those presenting with FSGS.…”

Section: Cytokine Alleles and Genotypes Correlate With Endstage Renalmentioning

confidence: 57%

“…A G to A polymorphism at position ª308 of the TNF-a promoter has been associated with increased TNF-a production and allograft rejection for renal, heart and lung transplants (3,10). We observed a nearly significant difference between Whites and Hispanics (p Ω 0.052) and Whites and Blacks (p Ω 0.058) in the distribution of TNF-a alleles.…”

Section: No Association Between Ethnicity and Inheritance Of The Polymentioning

confidence: 61%

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Ethnicity Greatly Influences Cytokine Gene Polymorphism Distribution

Hoffmann

Stanley

Cox

et al. 2002

American Journal of Transplantation

294

205

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Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of acute and chronic rejection. We have questioned whether ethnic-based differences in renal allograft survival could be due in part to inheritance of cytokine polymorphisms. To address that question, we studied the inheritance patterns for polymorphisms in several cytokine genes (IL-2, IL-6, IL-10, TNF-a, TGF-b, and IFNg) within an ethnically diverse study population comprised of 216 Whites, 58 Blacks, 25 Hispanics, and 31 Asians. Polymorphisms were determined by allele-specific polymerase chain reaction and restriction fragment length analysis. We found striking differences in the distribution of cytokine polymorphisms among ethnic populations. Specifically, significant differences existed between Blacks and both Whites and Asians in the distribution of the polymorphic alleles for IL-2. Blacks, Hispanics and Asians demonstrated marked differences in the inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Whites. Those of Asian descent exhibited an increase in IFN-g genotypes that result in low expression as compared to Whites. In contrast, we did not find significant ethnic-based differences in the inheritance of polymorphic alleles for TNF-a. Our results show that the inheritance of certain cytokine gene polymorphisms is strongly associated with ethnicity. These differences may contribute to the apparent influence of ethnicity on allograft outcome.

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Section: Discussioncontrasting

confidence: 58%

Section: Cytokine Alleles and Genotypes Correlate With Endstage Renalmentioning

confidence: 57%

Section: No Association Between Ethnicity and Inheritance Of The Polymentioning

confidence: 61%

See 1 more Smart Citation

Ethnicity Greatly Influences Cytokine Gene Polymorphism Distribution

Hoffmann

Stanley

Cox

et al. 2002

American Journal of Transplantation

294

205

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“…TNF2 was not associated with HLA A1, B8, and DR3, unlike in another study 17 and the allele frequency of TNF2 (0.037, nine of 238 alleles in this study) was much smaller than values reported for Caucasians (0.16-0.19). 16,20,25 This difference may be due to a difference of race, and partly explain the lower frequency of aGVHD in Japanese than in Western populations. 26,27 In this series, also, severe aGVHD occurred less frequently than has been reported in Western countries.…”

Section: Discussionmentioning

confidence: 99%

“…19 It has been reported that post-heart transplant patients with A at IL-10-1082 (low IL-10) and with TNF2 (high TNF-␣) were susceptible to graft rejection. 20 Furthermore, IL-10·G, a microsatellite polymorphic region at −1064 of the IL-10 promoter, 21 was suggested to play a role in the development of SLE since the distribution of the IL-10·G allele differed between SLE patients and healthy controls. 22 Such reports prompted us to investigate whether the gene polymorphisms of TNF-␣ and IL-10 are associated with the incidence of either severe aGVHD or cGVHD.…”

mentioning

confidence: 99%

Contribution of TNF-α and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation

Takahashi

Furukawa

Hashimoto

et al. 2000

Bone Marrow Transplant

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Summary:Some cytokines are believed to play a role in the development of acute and chronic GVHD after allo-hematopoietic stem cell transplantation. It has been reported that TNF-␣ and IL-10 gene polymorphisms are associated with the production of those cytokines and the development of graft failure after organ transplantation and systemic lupus erythematosus. We examined whether TNF-␣ and IL-10 gene polymorphisms affect the severity of acute GVHD (aGVHD) and chronic GVHD (cGVHD). Sixty-two and 54 patients were available for the analysis of aGVHD and cGVHD, respectively. We analyzed the gene polymorphisms derived from preand post-transplant blood cells. Donor-derived TNF2 allele (A) was more frequently detected in patients with aGVHD III/IV than those aGVHD 0-II (2/6 vs 2/56) (P ‫؍‬ 0.04). The donors of the patients with cGVHD more frequently possessed a greater number of alleles (allele 13 or more which contain 26 or more CA repeats) in IL-10·G than those without (13/26 vs 5/28) (P ‫؍‬ 0.02), and the patients with cGVHD had more CA repeats in donor-derived IL-10·G than those without (mean ‫؍‬ 25.2 vs 23.4) (P ‫؍‬ 0.01). Donor-derived TNF-308 and IL-10·G alleles may contribute to severe aGVHD and cGVHD, respectively, and will help us distinguish those patients at high risk for GVHD. Bone Marrow Transplantation (2000) 26, 1317-1323.

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Effect of size and dose on bone resorption activity of macrophages byin vitro clinically relevant ultra high molecular weight polyethylene particles

Green

Fisher

Matthews

et al. 2000

J. Biomed. Mater. Res.

301

203

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Polyethylene wear debris generated at the bearing surfaces of total artificial hip joints is thought to play an important role in the periprosthetic osteolysis and ultimately the aseptic loosening of these prostheses. The macrophage is believed to be central to this process by releasing various cytokines and other mediators of osteolysis upon phagocytosis of the polyethylene wear debris. This study evaluated the in vitro bone resorption response of C3H murine peritoneal macrophages to clinically relevant GUR 1120 polyethylene particles. Macrophages were co-cultured in vitro with GUR 1120 particles with a mean size of 0.24, 0.45, 1.71, and 7.62, and GUR 1120 polyethylene resin with a mean size of 88 microm at various particle volume (microm)(3): macrophage ratios (0.1:1; 1:1; 10:1; and 100:1). The conditioned supernatants were incubated with (45)calcium radio-labeled mouse calvariae, and bone resorption was measured as (45)calcium release. The results showed that the 0.24 microm particles stimulated the macrophages to generate bone resorbing activity at a ratio of 10(microm)(3) per macrophage. The 0.45 and 1.71 microm particles were active at a ratio of 100( microm)(3) per macrophage, and the 7.62 and 88 microm particles were inactive at all the doses tested. The co-culture supernatants were also assayed for TNF-alpha, IL-1beta, IL-6, and PGE(2). The results followed the same trend for particle size and volume dose to that observed for the bone resorbing activity. This study has demonstrated, for the first time, the importance of size and dose of clinically relevant polyethylene particles on the osteolytic response of macrophages in vitro.

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Cytokine Gene Polymorphism and Heart Transplant Rejection1

Abstract: We have identified a particular cytokine genotype that may confer susceptibility to increased levels of early rejection. Patients with a worse prognosis may be able to be identified pretransplant by DNA analysis of TNF-A, IL-10, and other gene polymorphisms.

Cited by 224 publications

References 8 publications

Ethnicity Greatly Influences Cytokine Gene Polymorphism Distribution

Ethnicity Greatly Influences Cytokine Gene Polymorphism Distribution

Contribution of TNF-α and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation

Effect of size and dose on bone resorption activity of macrophages byin vitro clinically relevant ultra high molecular weight polyethylene particles

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