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
Original Article

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.

Keywords

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

Notes

Acknowledgements

Many thanks to Xenofon Papanicolau and Tesfaye Mersha for help with Pathway analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

520_2018_4173_MOESM1_ESM.xlsx (31.9 mb)
ESM 1 (XLSX 32629 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Infectious DiseasesUniversity of CincinnatiCincinnatiUSA
  2. 2.Department of BiostatisticsUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Medical CenterUniversity of Arkansas for Medical SciencesLittle RockUSA
  4. 4.Department of GeneticsUniversity of Arkansas for Medical SciencesLittle RockUSA
  5. 5.Genomics Core Laboratory, Department of Biomedical InformaticsUniversity of Arkansas for Medical SciencesLittle RockUSA
  6. 6.Pharmaceutical SciencesUniversity of Arkansas for Medical SciencesLittle RockUSA

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