Analysis of 75 Candidate SNPs Associated With Acute Rejection in Kidney Transplant Recipients

Validation of rs2910164 in MicroRNA MIR146A

DeKAF Genomics and GEN03 Investigators

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Identifying kidney allograft recipients who are predisposed to acute rejection (AR) could allow for optimization of clinical treatment to avoid rejection and prolong graft survival. It has been hypothesized that a part of this predisposition is caused by the inheritance of specific genetic variants. There are many publications reporting a statistically significant association between a genetic variant, usually in the form of a single-nucleotide polymorphism (SNP), and AR. However, there are additional publications reporting a lack of this association when a different cohort of recipients is analyzed for the same single-nucleotide polymorphism. METHODS: In this report, we attempted to validate 75 common genetic variants, which have been previously reported to be associated with AR, using a large kidney allograft recipient cohort of 2390 European Americans and 482 African Americans. RESULTS: Of those variants tested, only 1 variant, rs2910164, which alters the expression of the microRNA MIR146A, was found to exhibit a significant association within the African American cohort. Suggestive variants were found in the genes CTLA and TLR4. CONCLUSIONS: Our results show that most variants previously reported to be associated with AR were not validated in our cohort. This shows the importance of validation when reporting the associations with complex clinical outcomes such as AR. Additional work will need to be done to understand the role of MIR146A in the risk of AR in kidney allograft recipients.

Original languageEnglish (US)
Pages (from-to)1591-1602
Number of pages12
JournalTransplantation
Volume103
Issue number8
DOIs
StatePublished - Aug 1 2019

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MicroRNAs
Single Nucleotide Polymorphism
Allografts
Kidney
African Americans
Graft Survival
Publications
Genes
Transplant Recipients
Therapeutics

PubMed: MeSH publication types

  • Journal Article

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Analysis of 75 Candidate SNPs Associated With Acute Rejection in Kidney Transplant Recipients : Validation of rs2910164 in MicroRNA MIR146A. / DeKAF Genomics and GEN03 Investigators.

In: Transplantation, Vol. 103, No. 8, 01.08.2019, p. 1591-1602.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Identifying kidney allograft recipients who are predisposed to acute rejection (AR) could allow for optimization of clinical treatment to avoid rejection and prolong graft survival. It has been hypothesized that a part of this predisposition is caused by the inheritance of specific genetic variants. There are many publications reporting a statistically significant association between a genetic variant, usually in the form of a single-nucleotide polymorphism (SNP), and AR. However, there are additional publications reporting a lack of this association when a different cohort of recipients is analyzed for the same single-nucleotide polymorphism. METHODS: In this report, we attempted to validate 75 common genetic variants, which have been previously reported to be associated with AR, using a large kidney allograft recipient cohort of 2390 European Americans and 482 African Americans. RESULTS: Of those variants tested, only 1 variant, rs2910164, which alters the expression of the microRNA MIR146A, was found to exhibit a significant association within the African American cohort. Suggestive variants were found in the genes CTLA and TLR4. CONCLUSIONS: Our results show that most variants previously reported to be associated with AR were not validated in our cohort. This shows the importance of validation when reporting the associations with complex clinical outcomes such as AR. Additional work will need to be done to understand the role of MIR146A in the risk of AR in kidney allograft recipients.",
author = "{DeKAF Genomics and GEN03 Investigators} and Oetting, {William S} and Schladt, {David P.} and Dorr, {Casey R.} and Baolin Wu and Weihua Guan and Remmel, {Rory P} and David Ikl{\'e} and Mannon, {Roslyn B.} and Matas, {Arthur J.} and Israni, {Ajay K.} and Jacobson, {Pamala A}",
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AU - DeKAF Genomics and GEN03 Investigators

AU - Oetting, William S

AU - Schladt, David P.

AU - Dorr, Casey R.

AU - Wu, Baolin

AU - Guan, Weihua

AU - Remmel, Rory P

AU - Iklé, David

AU - Mannon, Roslyn B.

AU - Matas, Arthur J.

AU - Israni, Ajay K.

AU - Jacobson, Pamala A

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AB - BACKGROUND: Identifying kidney allograft recipients who are predisposed to acute rejection (AR) could allow for optimization of clinical treatment to avoid rejection and prolong graft survival. It has been hypothesized that a part of this predisposition is caused by the inheritance of specific genetic variants. There are many publications reporting a statistically significant association between a genetic variant, usually in the form of a single-nucleotide polymorphism (SNP), and AR. However, there are additional publications reporting a lack of this association when a different cohort of recipients is analyzed for the same single-nucleotide polymorphism. METHODS: In this report, we attempted to validate 75 common genetic variants, which have been previously reported to be associated with AR, using a large kidney allograft recipient cohort of 2390 European Americans and 482 African Americans. RESULTS: Of those variants tested, only 1 variant, rs2910164, which alters the expression of the microRNA MIR146A, was found to exhibit a significant association within the African American cohort. Suggestive variants were found in the genes CTLA and TLR4. CONCLUSIONS: Our results show that most variants previously reported to be associated with AR were not validated in our cohort. This shows the importance of validation when reporting the associations with complex clinical outcomes such as AR. Additional work will need to be done to understand the role of MIR146A in the risk of AR in kidney allograft recipients.

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