Polymorphisms in cytokines and growth factor genes and their association with acute rejection and recurrence of hepatitis C virus disease in liver transplantation

Valeria Mas, R. A. Fisher, Daniel Maluf, K. J. Archer, M. J. Contos, S. A. Mills, M. L. Shiffman, D. S. Wilkinson, L. Oliveros, C. T. Garrett, Andrea Ferreira-Gonzalez

Research output: Contribution to journalArticle

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Abstract

Acute rejection (AR) and recurrence of hepatitis C virus (HCV) infection are complications after liver transplantation (LTx). Genetic factors play a role in cytokine production as a consequence of polymorphisms within cytokine genes. Our goal was to identify genetic factors that might be associated with AR and recurrence of HCV in liver transplant recipients (LTxRs). We studied 77 Caucasian LTxRs and 100 Caucasian healthy individuals. We studied single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-α [TNF-α, interleukin-6 (IL-6), IL-10, transforming growth factor-β1, and angiotensin-converting enzyme genes by SNaPSHOT™ Multiplex assay. SNPs were classified as high producers (HP), intermediate producers (IP), or low producers (LP), and their association with AR and recurrence of HCV were studied. The frequency of TNF-α IP and HP genotypes was significantly higher in LTxRs with AR in comparison to patients without AR (TNF-α HP -238: 63 vs 20%, p < 0.001; TNF-α HP -308: 47.4 vs 20%, p = 0.02). The frequency of IL-6 IP and HP genotypes was higher in patients with AR episodes, but the difference was not statistically significant (p = 0.14 . However, when we analyzed the simultaneous presence of pro-inflammatory genotypes in the same patient, we found a significant difference between patients with and without AR, respectively (42.1 vs 14.6 %, p = 0. 012). Moreover, the frequency of the IL-10 LP genotype was higher in LTx patients with AR (p = 0.001) compared to patients without AR. There was an association between pro-inflammatory genotypes and HCV recurrence. Our data suggest that cytokine gene polymorphisms might play a role in AR and HCV recurrence in LTxRs.

Original languageEnglish (US)
Pages (from-to)191-201
Number of pages11
JournalClinical Genetics
Volume65
Issue number3
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

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Virus Diseases
Hepacivirus
Liver Transplantation
Intercellular Signaling Peptides and Proteins
Cytokines
Recurrence
Genotype
Genes
Interleukin-10
Single Nucleotide Polymorphism
Interleukin-6
Transforming Growth Factors
Peptidyl-Dipeptidase A
Tumor Necrosis Factor-alpha
Liver

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Polymorphisms in cytokines and growth factor genes and their association with acute rejection and recurrence of hepatitis C virus disease in liver transplantation. / Mas, Valeria; Fisher, R. A.; Maluf, Daniel; Archer, K. J.; Contos, M. J.; Mills, S. A.; Shiffman, M. L.; Wilkinson, D. S.; Oliveros, L.; Garrett, C. T.; Ferreira-Gonzalez, Andrea.

In: Clinical Genetics, Vol. 65, No. 3, 01.03.2004, p. 191-201.

Research output: Contribution to journalArticle

Mas, V, Fisher, RA, Maluf, D, Archer, KJ, Contos, MJ, Mills, SA, Shiffman, ML, Wilkinson, DS, Oliveros, L, Garrett, CT & Ferreira-Gonzalez, A 2004, 'Polymorphisms in cytokines and growth factor genes and their association with acute rejection and recurrence of hepatitis C virus disease in liver transplantation', Clinical Genetics, vol. 65, no. 3, pp. 191-201. https://doi.org/10.1111/j.0009-9163.2004.00208.x
Mas, Valeria ; Fisher, R. A. ; Maluf, Daniel ; Archer, K. J. ; Contos, M. J. ; Mills, S. A. ; Shiffman, M. L. ; Wilkinson, D. S. ; Oliveros, L. ; Garrett, C. T. ; Ferreira-Gonzalez, Andrea. / Polymorphisms in cytokines and growth factor genes and their association with acute rejection and recurrence of hepatitis C virus disease in liver transplantation. In: Clinical Genetics. 2004 ; Vol. 65, No. 3. pp. 191-201.
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abstract = "Acute rejection (AR) and recurrence of hepatitis C virus (HCV) infection are complications after liver transplantation (LTx). Genetic factors play a role in cytokine production as a consequence of polymorphisms within cytokine genes. Our goal was to identify genetic factors that might be associated with AR and recurrence of HCV in liver transplant recipients (LTxRs). We studied 77 Caucasian LTxRs and 100 Caucasian healthy individuals. We studied single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-α [TNF-α, interleukin-6 (IL-6), IL-10, transforming growth factor-β1, and angiotensin-converting enzyme genes by SNaPSHOT™ Multiplex assay. SNPs were classified as high producers (HP), intermediate producers (IP), or low producers (LP), and their association with AR and recurrence of HCV were studied. The frequency of TNF-α IP and HP genotypes was significantly higher in LTxRs with AR in comparison to patients without AR (TNF-α HP -238: 63 vs 20{\%}, p < 0.001; TNF-α HP -308: 47.4 vs 20{\%}, p = 0.02). The frequency of IL-6 IP and HP genotypes was higher in patients with AR episodes, but the difference was not statistically significant (p = 0.14 . However, when we analyzed the simultaneous presence of pro-inflammatory genotypes in the same patient, we found a significant difference between patients with and without AR, respectively (42.1 vs 14.6 {\%}, p = 0. 012). Moreover, the frequency of the IL-10 LP genotype was higher in LTx patients with AR (p = 0.001) compared to patients without AR. There was an association between pro-inflammatory genotypes and HCV recurrence. Our data suggest that cytokine gene polymorphisms might play a role in AR and HCV recurrence in LTxRs.",
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AU - Contos, M. J.

AU - Mills, S. A.

AU - Shiffman, M. L.

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AU - Garrett, C. T.

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