Single-nucleotide polymorphisms, acute rejection, and severity of tubulitis in kidney transplantation, accounting for center-to-center variation

Ajay Israni, Robert Leduc, John Holmes, Pamala A. Jacobson, Vishal Lamba, Weihua Guan, David Schladt, Jinbo Chen, Arthur J. Matas, William S. Oetting

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Background. Acute rejection (AR) is associated with worse renal allograft outcomes. Therefore, this study investigated single-nucleotide polymorphisms (SNPs) to identify genetic variants associated with AR, accounting for center variation, in a multicenter, prospective, observation study. Methods. We enrolled patients from six transplant centers, five in the United States and one in Canada. A total of 2724 SNPs were genotyped. We accounted for center variation in AR rates by stratifying by transplant center and using novel knowledge discovery methods. Results. There was significant center variation in AR rates across the six transplant sites (P<0.0001). Accounting for this difference and clinical factors independently associated with AR, we identified 15 novel SNPs associated with AR with stratification by transplant center (P<0.05). We also identified 15 novel SNPs associated with severity of tubulitis scores, after adjusting for transplant center and other clinical factors independently associated with severity of tubulitis (P<0.05). There was some overlap with one SNP associated with AR and also associated with severity of tubulitis, among the top 15 SNPs. Conclusion. Center-to-center variation is a major challenge to genomic studies focused on AR. The SNPs associated with AR and severity of tubulitis in this study will need to be validated in independent cohort of kidney transplant recipients.

Original languageEnglish (US)
Pages (from-to)1401-1408
Number of pages8
JournalTransplantation
Volume90
Issue number12
DOIs
StatePublished - Dec 27 2010
Externally publishedYes

Keywords

  • Acute rejection
  • Single-nucleotide polymorphisms
  • Tubulitis

ASJC Scopus subject areas

  • Transplantation

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