A systematic review of single nucleotide polymorphisms affecting allopurinol pharmacokinetics and serum uric acid level

Pharmacogenomics. 2024;25(10-11):479-494. doi: 10.1080/14622416.2024.2403969. Epub 2024 Sep 30.

Abstract

Aim: To summarize the effects of single nucleotide polymorphisms (SNPs) on the pharmacokinetics of allopurinol to control uric acid levels.Methods: A comprehensive search was conducted in PubMed, Web of Science and Scopus databases from inception to January 2024, includes 17 articles focusing on SNPs and pharmacokinetics of allopurinol and oxypurinol.Results: A total of 11 SNPs showed a significant association with pharmacokinetics of allopurinol and oxypurinol, as well as their potential clinical implications.Conclusion: SNPs in ATP-binding cassette super-family G member 2 (ABCG2), solute carrier family 2 member 9 (SLC2A9), solute carrier family 17 member 1 (SLC17A1), solute carrier family 22 member 12 (SLC22A12), solute carrier family 22 member 13 (SLC22A13) and PDZ domain containing 1 (PDZK1) genes were associated with allopurinol clearance, while SNPs in aldehyde oxidase 1 (AOX1) genes involved in metabolism of allopurinol. SNPs in gremlin 2, DAN family BMP antagonist (GREM2) gene impacted uric acid control, but the specific mechanism governing the expression of GREM2 remains unknown. Our study indicated that the identified SNPs show contradictory effects, reflecting inconsistencies and differences observed across various studies.

Keywords: SNPs; allopurinol; clearance; oxypurinol; pharmacokinetics; single nucleotide polymorphisms; uric acid level.

Plain language summary

[Box: see text].

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Allopurinol* / pharmacokinetics
  • Allopurinol* / therapeutic use
  • Gout Suppressants / pharmacokinetics
  • Gout Suppressants / therapeutic use
  • Humans
  • Polymorphism, Single Nucleotide* / genetics
  • Uric Acid* / blood

Substances

  • Allopurinol
  • Uric Acid
  • Gout Suppressants