The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection
The −308G/A SNP of tumor necrosis factor-alpha (TNF-α) gene affects TNF-α production. As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/2197595 |
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| author | Ana Isabel Sánchez-Fructuoso Isabel Pérez-Flores Rosalia Valero Maria Angeles Moreno Miguel Fernandez-Arquero Elena Urcelay Cristina Fernández-Pérez Jose Luis Santiago |
| author_facet | Ana Isabel Sánchez-Fructuoso Isabel Pérez-Flores Rosalia Valero Maria Angeles Moreno Miguel Fernandez-Arquero Elena Urcelay Cristina Fernández-Pérez Jose Luis Santiago |
| author_sort | Ana Isabel Sánchez-Fructuoso |
| collection | DOAJ |
| description | The −308G/A SNP of tumor necrosis factor-alpha (TNF-α) gene affects TNF-α production. As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups (discovery and validation cohorts) was performed to identify the best predictors of acute rejection (AR). The effect on transplant outcome was analyzed by an adjusted logistic regression model. Carriers of the A allele, associated with elevated TNF-α production, presented a higher risk of AR (OR = 2.78; 95% CI = 1.40–5.51). Logistic regression analyses for AR showed an interaction between the polymorphism and treatment with thymoglobulin (p-interaction = 0.03). In recipients who did not receive thymoglobulin, carriers of A allele had higher risk of AR (OR = 4.05; 95% CI = 1.76–9.28). Moreover, carriers of A allele not treated with thymoglobulin presented higher risk of AR than those who received thymoglobulin (OR = 13.74; 95% CI = 1.59–118.7). The AUC of the model in the discovery cohort was 0.70 and in the validation cohort was 0.69. Our findings indicate that the −308G/A TNF-α polymorphism is associated with AR risk and it modulates the effectiveness of thymoglobulin treatment. This pharmacogenetic effect lets us propose this SNP as a useful predictor biomarker to tailor immunosuppressive regimens. |
| format | Article |
| id | doaj-art-8ef08c55758f45a48330cc8c12b16255 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-8ef08c55758f45a48330cc8c12b162552025-02-03T06:06:03ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/21975952197595The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute RejectionAna Isabel Sánchez-Fructuoso0Isabel Pérez-Flores1Rosalia Valero2Maria Angeles Moreno3Miguel Fernandez-Arquero4Elena Urcelay5Cristina Fernández-Pérez6Jose Luis Santiago7Nephrology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, SpainNephrology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, SpainNephrology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, SpainNephrology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, SpainImmunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, SpainImmunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, SpainClinical Research and Methodology Unit, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, SpainImmunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, SpainThe −308G/A SNP of tumor necrosis factor-alpha (TNF-α) gene affects TNF-α production. As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups (discovery and validation cohorts) was performed to identify the best predictors of acute rejection (AR). The effect on transplant outcome was analyzed by an adjusted logistic regression model. Carriers of the A allele, associated with elevated TNF-α production, presented a higher risk of AR (OR = 2.78; 95% CI = 1.40–5.51). Logistic regression analyses for AR showed an interaction between the polymorphism and treatment with thymoglobulin (p-interaction = 0.03). In recipients who did not receive thymoglobulin, carriers of A allele had higher risk of AR (OR = 4.05; 95% CI = 1.76–9.28). Moreover, carriers of A allele not treated with thymoglobulin presented higher risk of AR than those who received thymoglobulin (OR = 13.74; 95% CI = 1.59–118.7). The AUC of the model in the discovery cohort was 0.70 and in the validation cohort was 0.69. Our findings indicate that the −308G/A TNF-α polymorphism is associated with AR risk and it modulates the effectiveness of thymoglobulin treatment. This pharmacogenetic effect lets us propose this SNP as a useful predictor biomarker to tailor immunosuppressive regimens.http://dx.doi.org/10.1155/2016/2197595 |
| spellingShingle | Ana Isabel Sánchez-Fructuoso Isabel Pérez-Flores Rosalia Valero Maria Angeles Moreno Miguel Fernandez-Arquero Elena Urcelay Cristina Fernández-Pérez Jose Luis Santiago The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection Journal of Immunology Research |
| title | The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection |
| title_full | The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection |
| title_fullStr | The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection |
| title_full_unstemmed | The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection |
| title_short | The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection |
| title_sort | polymorphism 308g a of tumor necrosis factor α gene modulates the effect of immunosuppressive treatment in first kidney transplant subjects who suffer an acute rejection |
| url | http://dx.doi.org/10.1155/2016/2197595 |
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