Senu Apewokin1, Jeannette Y Lee2, Julia A Goodwin3, Kent D McKelvey4, Owen W Stephens5, Daohong Zhou6, Elizabeth Ann Coleman3. 1. Division of Infectious Diseases, University of Cincinnati, 231 Albert Sabin Way, MSB 6153B, Cincinnati, OH, USA. senukobla@yahoo.com. 2. Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 3. Medical Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 4. Department of Genetics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 5. Genomics Core Laboratory, Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 6. Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
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.
BACKGROUND:Clostridium difficileinfection (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.
Authors: Melinda A Engevik; Mary Beth Yacyshyn; Kristen A Engevik; Jiang Wang; Benjamin Darien; Daniel J Hassett; Bruce R Yacyshyn; Roger T Worrell Journal: Am J Physiol Gastrointest Liver Physiol Date: 2014-12-31 Impact factor: 4.052
Authors: Jiang Li; Yanfei Zhang; Alexandria L Jilg; Donna M Wolk; Harshit S Khara; Amy Kolinovsky; David D K Rolston; Raquel Hontecillas; Josep Bassaganya-Riera; Marc S Williams; Vida Abedi; Ming Ta Michael Lee Journal: Front Immunol Date: 2021-03-25 Impact factor: 7.561