Next Article in Journal / Special Issue
Primary Obsessive Slowness: A Complex Presentation and Treatment Difficulties
Previous Article in Journal / Special Issue
Single Cell Plant Model of Equisetum arvense for the Study Antihistamine Effects of Azulene and Sesquiterpene Lactones
 
 
Review

Pharmacogenetic Perspective for Optimal Gout Management

Department of Pharmacotherapy and Outcome Science, School of Pharmacy, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA 23298, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Fabrizio Schifano and Francisco Abad Santos
Future Pharmacol. 2022, 2(2), 135-152; https://doi.org/10.3390/futurepharmacol2020011
Received: 27 February 2022 / Revised: 29 April 2022 / Accepted: 1 May 2022 / Published: 9 May 2022
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
Pharmacogenetics (PGx) is an emerging field of pharmacology focusing on how gene variations affect the patient’s response to treatment. Pharmacogenetics is a promising tool to optimize the selection and dosing of medications, including urate-lowering therapies (ULTs) among patients with gout. The global prevalence of gout is rising, and it disproportionately affects specific racial groups and individuals with select socioeconomic status. Genetic and experimental findings have provided evidence that genetic polymorphisms associated with serum urate pathology are also of pharmacogenetic interest. Patients with gout present with several comorbidities, warranting the use of several acute and long-term medications that increase their pill burden and the risk of adverse drug events. Implementing PGx testing can identify individuals who are more or less likely to benefit from a given treatment, improve medication adherence, and reduce pill burden. The purpose of this non-systematic review was to evaluate the contemporary evidence for PGx use in gout management, especially treatment modalities associated with specific genetic polymorphisms that could impact medication safety and efficacy. Strong evidence suggests that individuals carrying the HLA-B*58:01 allele are at a higher risk of serious and life-threatening skin reactions when taking allopurinol. Additionally, racial disparities in the frequency of HLA-B*58:01 warrant genetic screening in high-risk populations, specifically some Asian subgroups and African Americans. Individuals that are G6PD-deficient can develop hemolytic anemia and methemoglobinemia with pegloticase and probenecid use. Patients with the less active form of the drug-metabolizing CYP2C9 are at higher risk for NSAID-related upper gastrointestinal (GI) bleeding. Emerging evidence of clinically significant drug-gene pairs among various gout therapies is growing. Genes found to modulate the response to allopurinol include AOX, ABCG2, and SLC22A12. Meanwhile, UGT1A1 appears to modulate the response to Febuxostat. While CYP2C9 may modulate the toxicity of benzbromarone, SLC22A12 and ABCB1 were found to modulate the response to both benzbromarone and probenecid. The genes CYP2D6, ABCB1, gene cluster (rs6916345 G>A), and SEPHS1 were recently reported to modulate the safety and efficacy of colchicine. Finally, HCG22 and IL1RN are linked with the response to corticosteroid and anakinra, respectively. This review examines and synthesizes the most current level of evidence for using PGx to maximize gout pharmacotherapy. View Full-Text
Keywords: gout; pharmacogenetics; precision medicine; genetics; urate transportome; G6PD; HLA-B*58:01; CYP2C9; allopurinol; urate-lowering therapy; NSAIDs; colchicine; CPIC; FDA; PharmGKB gout; pharmacogenetics; precision medicine; genetics; urate transportome; G6PD; HLA-B*58:01; CYP2C9; allopurinol; urate-lowering therapy; NSAIDs; colchicine; CPIC; FDA; PharmGKB
Show Figures

Graphical abstract

MDPI and ACS Style

Alrajeh, K.Y.; Roman, Y.M. Pharmacogenetic Perspective for Optimal Gout Management. Future Pharmacol. 2022, 2, 135-152. https://doi.org/10.3390/futurepharmacol2020011

AMA Style

Alrajeh KY, Roman YM. Pharmacogenetic Perspective for Optimal Gout Management. Future Pharmacology. 2022; 2(2):135-152. https://doi.org/10.3390/futurepharmacol2020011

Chicago/Turabian Style

Alrajeh, Khalifa Y., and Youssef M. Roman. 2022. "Pharmacogenetic Perspective for Optimal Gout Management" Future Pharmacology 2, no. 2: 135-152. https://doi.org/10.3390/futurepharmacol2020011

Find Other Styles

Article Access Map by Country/Region

1
Back to TopTop