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PLoS One. 2015 Jun 1;10(6):e0127791. doi: 10.1371/journal.pone.0127791. eCollection 2015.

Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy.

Author information

1
Department of Pediatrics, Vanderbilt University School of Medicine and the Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, United States of America.
2
Department of Pediatrics, Vanderbilt University School of Medicine and the Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, United States of America; Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America.
3
Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, Tennessee, United States of America.
4
Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, United States of America.
5
Center for Human Genetics, Marshfield Clinic, Marshfield, Wisconsin, United States of America.
6
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
7
Institute for Clinical and Translational Research, Vanderbilt University, Nashville, Tennessee, United States of America.
8
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America.
9
School of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
10
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
11
Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America.
12
Department of Pharmaceutical Services, Vanderbilt University, Nashville, Tennessee, United States of America.
13
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
14
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America; Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, United States of America.

Abstract

Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, β = -0.06, p = 1.1 x 10(-7)). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 x 10(-7). Variation in this region on chromosome 6, which includes the genes TBC1D32/C6orf170 and GJA1 (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.

PMID:
26030142
PMCID:
PMC4452656
DOI:
10.1371/journal.pone.0127791
[Indexed for MEDLINE]
Free PMC Article

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