Host genetic susceptibility to Clostridium difficile infections in patients undergoing autologous stem cell transplantation: a genome-wide association study

Senu Apewokin, Jeannette Y. Lee, Julia A. Goodwin, Kent D. McKelvey, Owen W. Stephens, Daohong Zhou, Elizabeth Ann Coleman

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Clostridium difficile infection (CDI) is the most common hospital-acquired infection. Unfortunately, genes that identify CDI-susceptible patients have not been well described. We performed a genome-wide association study (GWAS) to determine genetic variants associated with the development of CDI. Methods: A cohort study of Caucasian patients undergoing autologous stem cell transplantation for multiple myeloma was performed. Patients were genotyped using Illumina® Whole Genome Genotyping Infinium chemistry. We then compared CDI-positive to CDI-negative patients using logistic regression for baseline clinical factors and false discovery rate (FDR) for genetic factors [single nucleotide polymorphisms (SNPs)]. SNPs associated with CDI at FDR of p < 0.01 were then incorporated into a logistic regression model combining clinical and genetic factors. Results: Of the 646 patients analyzed (59.7% male), 57 patients were tested CDI positive (cases) and were compared to 589 patients who were tested negative (controls). Hemoglobin, albumin, and hematocrit were lower for cases (p < 0.05). Eight SNPs on five genes (FLJ16171, GORASP2, RLBP1L1, ASPH, ATP7B) were associated with CDI at FDR p < 0.01. In the combined clinical and genetic model, low albumin and three genes RLBP1L1, ASPH, and ATP7B were associated with CDI. Conclusion: Low serum albumin and genes RLBP1L1 and ASPH located on chromosome 8 and ATP7B on chromosome 13 were associated with CDI. Of particular interest is ATP7B given its copper modulatory role and the sporicidal properties of copper against Clostridium difficile.

Original languageEnglish (US)
Pages (from-to)3127-3134
Number of pages8
JournalSupportive Care in Cancer
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2018
Externally publishedYes

Keywords

  • Cancer
  • Chemotherapy
  • Clostridium difficile
  • Genome wide association study
  • Pathophysiology
  • Stem cell transplantation

ASJC Scopus subject areas

  • Oncology

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