Program Schedule

438
Genetic Variants Associated with the Development of Clostridium Difficile Infection during Autologous Stemcell Transplantation

Session: Poster Abstract Session: Transplant Infectious Diseases
Thursday, October 9, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background: Genetic susceptibility has been thought to contribute to development of infectious diseases in immunocompromised hosts. Clostridium difficile infection (CDI) confers considerable morbidity and mortality during stemcell transplantation (SCT). Unfortunately genes that identify CDI-susceptible SCT recipients have not been well described. We performed a genome wide association study in an effort to determine genetic variants associated with the development of CDI in autologous SCT (ASCT) recipients

Methods:  Patients undergoing ASCT for multiple myeloma were genotyped using Illumina’s HumanOmni1-Quad v1.0 BeadChip and 1,000, 000 SNPs were tested for association with development of CDI. CDI testing was performed utilizing ELISA for toxin A &B. We then compared baseline clinical characteristics using logistic regression and genetic factors (SNPs) utilizing a false discovery rate (FDR) approach between the two groups. SNPs associated with CDI at FDR of p<0.01 were evaluated. These SNPs were then incorporated into a logistic regression model combining clinical and genetic factors

Results: 646 pts met study criteria and of these 59.7% were male. Mean Age & GFR were 57.77±9.12 yrs and 78.30±38.63 ml/min resp.  Fifty-seven (57) pts tested CDI positive and were compared to 589 test-negative controls. Comparison of means± SD between cases and controls for select clinical characteristics were as follows; hemoglobin 10.50±1.45 vs 11.01±1.45 p=0.019; hematocrit 31.90±4.45 vs 33.35±4.45 p=0.011; serum albumin 3.59 ±0.58 vs 3.94 ± 0.51 p<0.001. For the genetic comparison seven SNPs on four 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,ATP7B were assoc. with CDI

Conclusion: In this study low serum albumin in addition to genes RLBP1L1,ASPH, located on chromosome 8 and ATP7B on chromosome 13 conferred susceptibility to CDI

Senu Apewokin, MD1, Elizabeth Coleman, PhD2, Carol Enderlin, PhD2, Julia Goodwin, PhD2, Jeannette Lee, PhD2, Stephen Erickson, PhD2, Kent Mckelvey, MD, PhD2, Vinay Raj, PhD2, Naveen Sanath Kumar, MD1 and Zhou Daohong, PhD2, (1)The Myeloma Institute for Research and Therapy/University of Arkansas for Medical Sciences, Little Rock, AR, (2)University of Arkansas for Medical Sciences, Little Rock, AR

Disclosures:

S. Apewokin, T 2 biosystem: Investigator, Research grant
Viracor: Investigator, Research grant

E. Coleman, None

C. Enderlin, None

J. Goodwin, None

J. Lee, None

S. Erickson, None

K. Mckelvey, None

V. Raj, None

N. Sanath Kumar, None

Z. Daohong, None

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