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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chromosomes, Human / genetics
  • Chromosomes, Human, Pair 6 / genetics
  • Connexin 43 / genetics
  • Creatinine / blood*
  • Female
  • GTPase-Activating Proteins / genetics
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Vancomycin / therapeutic use*

Substances

  • Connexin 43
  • GJA1 protein, human
  • GTPase-Activating Proteins
  • TBC1D32 protein, human
  • Vancomycin
  • Creatinine