Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1080/15287394.2017.1286922 http://hdl.handle.net/11449/178881 |
Resumo: | Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype–gene expression associations were also assessed. Peripheral blood samples were used for genotyping of 24 SNPs on the following genes: CYP3A4, CYP3A5, CYP2E1, POR, UGT2B7, UGT1A9, ABCB1, ABCC2, ABCG2, SLCO1B1, TNF, IL2, IRF5, TGFB1, NFKBIA, IL10, IL23R, NFAT, and CCR5 by real-time PCR. The analysis of gene expression was performed by RT-qPCR. The association between graft rejection episodes and polymorphic variants was assessed using odds ratios. Polymorphisms rs7662029 (UGT2B7) and rs6714486 (UGT1A9) were associated with occurrence of graft rejection episodes, rs7662029 (UGT2B7) exhibited a protective effect (1.85-fold), and rs6714486 (UGT1A9) an increased 1.6-fold increased risk of graft rejection. Among drug transporter genes, only rs2231142 (ABCG2) demonstrated an association with a 1.92-fold decrease in the risk of graft rejection. The immunological SNP rs10889677 (IL23R) was associated with a 1.9-fold enhanced risk of graft rejection. Association between genotypes and gene expression was not detected. Therefore, SNPs of UGT2B7, UGT1A9, ABCG2, and IL23R genes may be useful as candidate markers for screening of risk graft rejection in renal transplant patients. These markers may improve medical decisions, avoiding adverse effects. |
id |
UNSP_52dd6c469ae3845c64bf1918d3af86ed |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/178881 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patientsDespite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype–gene expression associations were also assessed. Peripheral blood samples were used for genotyping of 24 SNPs on the following genes: CYP3A4, CYP3A5, CYP2E1, POR, UGT2B7, UGT1A9, ABCB1, ABCC2, ABCG2, SLCO1B1, TNF, IL2, IRF5, TGFB1, NFKBIA, IL10, IL23R, NFAT, and CCR5 by real-time PCR. The analysis of gene expression was performed by RT-qPCR. The association between graft rejection episodes and polymorphic variants was assessed using odds ratios. Polymorphisms rs7662029 (UGT2B7) and rs6714486 (UGT1A9) were associated with occurrence of graft rejection episodes, rs7662029 (UGT2B7) exhibited a protective effect (1.85-fold), and rs6714486 (UGT1A9) an increased 1.6-fold increased risk of graft rejection. Among drug transporter genes, only rs2231142 (ABCG2) demonstrated an association with a 1.92-fold decrease in the risk of graft rejection. The immunological SNP rs10889677 (IL23R) was associated with a 1.9-fold enhanced risk of graft rejection. Association between genotypes and gene expression was not detected. Therefore, SNPs of UGT2B7, UGT1A9, ABCG2, and IL23R genes may be useful as candidate markers for screening of risk graft rejection in renal transplant patients. These markers may improve medical decisions, avoiding adverse effects.Department of General Biology Center of Biological Sciences State University of LondrinaCenter of Health Sciences State University of LondrinaFaculty of Medicine São Paulo State University (UNESP)Department of Clinical Genetics Vejle Hospital DK and University of Southern DenmarkFaculty of Medicine São Paulo State University (UNESP)Universidade Estadual de Londrina (UEL)Universidade Estadual Paulista (Unesp)DK and University of Southern DenmarkCilião, Heloísa LizottiCamargo-Godoy, Rossana Batista Oliveirade Souza, Marilesia Ferreirados Reis, Mariana Bisarro [UNESP]Iastrenski, LorenaAlvares Delfino, Vinicius DaherRogatto, Silvia Regina [UNESP]de Syllos Cólus, Ilce Mara2018-12-11T17:32:31Z2018-12-11T17:32:31Z2017-08-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article661-671application/pdfhttp://dx.doi.org/10.1080/15287394.2017.1286922Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 80, n. 13-15, p. 661-671, 2017.1087-26201528-7394http://hdl.handle.net/11449/17888110.1080/15287394.2017.12869222-s2.0-850195887732-s2.0-85019588773.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Toxicology and Environmental Health - Part A: Current Issues0,8880,888info:eu-repo/semantics/openAccess2024-09-03T14:30:11Zoai:repositorio.unesp.br:11449/178881Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T14:30:11Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients |
title |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients |
spellingShingle |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients Cilião, Heloísa Lizotti |
title_short |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients |
title_full |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients |
title_fullStr |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients |
title_full_unstemmed |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients |
title_sort |
Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients |
author |
Cilião, Heloísa Lizotti |
author_facet |
Cilião, Heloísa Lizotti Camargo-Godoy, Rossana Batista Oliveira de Souza, Marilesia Ferreira dos Reis, Mariana Bisarro [UNESP] Iastrenski, Lorena Alvares Delfino, Vinicius Daher Rogatto, Silvia Regina [UNESP] de Syllos Cólus, Ilce Mara |
author_role |
author |
author2 |
Camargo-Godoy, Rossana Batista Oliveira de Souza, Marilesia Ferreira dos Reis, Mariana Bisarro [UNESP] Iastrenski, Lorena Alvares Delfino, Vinicius Daher Rogatto, Silvia Regina [UNESP] de Syllos Cólus, Ilce Mara |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Londrina (UEL) Universidade Estadual Paulista (Unesp) DK and University of Southern Denmark |
dc.contributor.author.fl_str_mv |
Cilião, Heloísa Lizotti Camargo-Godoy, Rossana Batista Oliveira de Souza, Marilesia Ferreira dos Reis, Mariana Bisarro [UNESP] Iastrenski, Lorena Alvares Delfino, Vinicius Daher Rogatto, Silvia Regina [UNESP] de Syllos Cólus, Ilce Mara |
description |
Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype–gene expression associations were also assessed. Peripheral blood samples were used for genotyping of 24 SNPs on the following genes: CYP3A4, CYP3A5, CYP2E1, POR, UGT2B7, UGT1A9, ABCB1, ABCC2, ABCG2, SLCO1B1, TNF, IL2, IRF5, TGFB1, NFKBIA, IL10, IL23R, NFAT, and CCR5 by real-time PCR. The analysis of gene expression was performed by RT-qPCR. The association between graft rejection episodes and polymorphic variants was assessed using odds ratios. Polymorphisms rs7662029 (UGT2B7) and rs6714486 (UGT1A9) were associated with occurrence of graft rejection episodes, rs7662029 (UGT2B7) exhibited a protective effect (1.85-fold), and rs6714486 (UGT1A9) an increased 1.6-fold increased risk of graft rejection. Among drug transporter genes, only rs2231142 (ABCG2) demonstrated an association with a 1.92-fold decrease in the risk of graft rejection. The immunological SNP rs10889677 (IL23R) was associated with a 1.9-fold enhanced risk of graft rejection. Association between genotypes and gene expression was not detected. Therefore, SNPs of UGT2B7, UGT1A9, ABCG2, and IL23R genes may be useful as candidate markers for screening of risk graft rejection in renal transplant patients. These markers may improve medical decisions, avoiding adverse effects. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-08-03 2018-12-11T17:32:31Z 2018-12-11T17:32:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1080/15287394.2017.1286922 Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 80, n. 13-15, p. 661-671, 2017. 1087-2620 1528-7394 http://hdl.handle.net/11449/178881 10.1080/15287394.2017.1286922 2-s2.0-85019588773 2-s2.0-85019588773.pdf |
url |
http://dx.doi.org/10.1080/15287394.2017.1286922 http://hdl.handle.net/11449/178881 |
identifier_str_mv |
Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 80, n. 13-15, p. 661-671, 2017. 1087-2620 1528-7394 10.1080/15287394.2017.1286922 2-s2.0-85019588773 2-s2.0-85019588773.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Toxicology and Environmental Health - Part A: Current Issues 0,888 0,888 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
661-671 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
_version_ |
1810021384164737024 |