Pharmacogenomics of Leukotriene Modifiers: A Systematic Review and Meta-Analysis

Area of Science:

• Pharmacogenetics
• Asthma Treatment
• Genomic Medicine

Background:

• Pharmacogenetics of leukotriene modifiers (LTMs) for asthma is rapidly evolving.
• Clinical application of pharmacogenetic testing for LTMs is not yet established.
• Systematic review and meta-analysis to evaluate pharmacogenomics impact on LTMs response.

Purpose of the Study:

• To systematically review and meta-analyze the impact of pharmacogenomics on leukotriene modifier response in asthma patients.
• To identify specific genetic variations influencing treatment efficacy.
• To assess the clinical relevance of pharmacogenetic findings for LTMs.

Main Methods:

• Systematic search of PubMed, EMBASE, and Cochrane databases for studies published until May 2022.
• Inclusion of pharmacogenomics/genetics studies of asthma patients using LTMs.
• Meta-analysis performed using Review Manager and R software on data from 31 studies (8084 participants).

Main Results:

• Two genome-wide association studies (GWAS) yielded differing results; no overlap with candidate gene SNPs.
• Candidate gene studies focused on ALOX5, LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149) with inconsistent conclusions.
• LTC4S-444A/C polymorphism showed no significant overall effect, but AA homozygotes had reduced lung function improvements in subgroups using non-selective CysLT receptor antagonists or LTMs without inhaled corticosteroids (ICS).

Conclusions:

• Significant variability exists in the pharmacogenomics of LTMs treatment response.
• The LTC4S-444A/C polymorphism may influence treatment response in asthma patients using non-selective CysLT receptor antagonists or LTMs without ICS.
• Further research is necessary to validate the pharmacogenomic influence on LTMs response in asthma.