The impact of the solute carrier gene superfamily polymorphisms on tyrosine kinase inhibitors responses among chronic myeloid leukemia: A meta-analysis

Background

Tyrosine kinase inhibitors (TKIs) are currently the first-line therapy for chronic myeloid leukemia (CML), but proportion of treatment responses may be influenced by genetic polymorphisms, especially, the solute carrier gene superfamily (SLC). This study was conducted to evaluate the relationship of polymorphisms in the SLC genes family and treatment responses to TKIs among CML patients.

Methods

A systematic search was conducted from four databases, including PubMed, Cochrane Library, Embase and Web of Science, up to March 2023. The relationship between SLC polymorphisms and TKI efficacy was assessed by pooled odds ratios (ORs) of the complete cytogenetic response (CCyR) and major molecular biological response (MMR) with 95 % confidence intervals (95 %CIs) across five genetic models (dominant, recessive, homozygote, heterozygote, and allele). Meta-analyses, heterogeneity between studies, publication bias, sensitivity, meta-regression and subgroup analysis were all performed.

Results

A total of 19/983 studies meeting the criteria were included in the meta-analysis, with eight variants belonging to three genes (SLC22A1, SLCO1B3, and SLC22A4). The results showed that there was a statistically significant association between the SLC22A1 rs683369 variant and a lower rate of achieving MMR in all 05 genetic models. Similar results were also recorded in the dominant and homozygote models of the SLC22A1 rs628031 variant (OR= 0.61 (95 %CI= 0.46–0.82); OR= 0.46 (95 %CI= 0.23–0.94), respectively); particularly in Asian patients. No relationship was identified between MMR and other genes, as well as that of CCyR and all variants.

Conclusion

SLC variants can be predictive signals of imatinib responses among CML; Asian patients should be paid attention during the treatment.