Host genetic susceptibility to Clostridium difficile infections in patients undergoing autologous stem cell transplantation: a genome-wide association study
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.
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.
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.
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.
KeywordsClostridium difficile Pathophysiology Stem cell transplantation Genome wide association study Chemotherapy Cancer
Many thanks to Xenofon Papanicolau and Tesfaye Mersha for help with Pathway analysis.
Financial support to Elizabeth Ann Coleman was provided by the National Institutes of Health (NIH)/National Institute of Nursing Research (NINR) 5 RC2NR011945, and for additional support, the Translational Research Institute at UAMS (grant no. 1UL1RR029884) and the Elizabeth Stanley Cooper Chair in Oncology Nursing.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
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