Van Driest SL, McGregor TL, Velez Edwards DR, Saville BR, Kitchner TE, Hebbring SJ, Brilliant M, Jouni H, Kullo IJ, Creech CB, Kannankeril PJ, Vear SI, Brothers KB, Bowton EA, Shaffer CM, Patel N, Delaney JT, Bradford Y, Wilson S, Olson LM, Crawford DC, Potts AL, Ho RH, Roden DM, Denny JC. Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy. PloS one. 10(10). e0127791. PMID: 26030142 [PubMed] PMCID: PMC4452656
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.