AUTHOR=Dai Xiaona , Yuan Fang , Chai Lan 

TITLE=Meta-analysis of the effects of CYP3A5*3 gene polymorphisms on tacrolimus blood concentration and effectiveness in Chinese patients with membranous nephropathy

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1385322

DOI=10.3389/fphar.2024.1385322

ISSN=1663-9812

ABSTRACT=<sec><title>Objective</title><p>The study aimed to systematically evaluate the relationship between CYP3A5*3 gene polymorphisms and the blood concentration and effectiveness of tacrolimus (TAC) in patients with membranous nephropathy (MN).</p></sec><sec><title>Methods</title><p>PubMed, Cochrane Library, Embase, Web of Science, China Biomedical, China National Knowledge Infrastructure, Wanfang, Vipshop, ReadShow, Clinical Trials Registry, and other databases were searched. Studies on the relationship between CYP3A5*3 gene polymorphism and TAC blood concentration in MN patients were collected, and meta-analysis was performed using Stata 16 software. </p></sec><sec><title>Results</title><p>A total of eight publications were included in the study, including 498 MN patients. CYP3A5*3 gene polymorphisms are associated with tacrolimus blood levels in patients with MN. The results of the relationship between CYP3A5*3 genotype polymorphisms and tacrolimus blood trough concentrations of the AA + AG genotype were lower than those of the GG genotype at ≤1 month [WMD = −2.08, 95% CI (−2.57, −1.59), <italic>p</italic> &lt; 0.001] and 1–6 months [WMD = −0.63, 95% CI (−0.98, −0.27), <italic>p</italic> &lt; 0.001]; however, they were not statistically significant at ≥6 months (<italic>p</italic> = 0.211). Furthermore, the subgroup analysis revealed that the dose-adjusted concentration of tacrolimus (C0/D) of the AA + AG genotype was lower than that of the GG genotype at ≤1 month [SMD = −1.93, 95% CI (−2.79, −1.08), <italic>p</italic> &lt; 0.001], 1–6 months [SMD = −2.25, 95% CI (−2.71, −1.79), <italic>p</italic> &lt; 0.001], and ≥6 months [SMD = −2.36, 95% CI (−2.86, −1.86), <italic>p</italic> &lt; 0.001]. In addition, there was no statistically significant difference in effectiveness between the two groups at 3, 6, and 12 months of TAC administration (<italic>p</italic> &gt; 0.05).</p></sec><sec><title>Conclusion</title><p>Serum TAC concentrations in MN patients were correlated with CYP3A5*3 genotype polymorphisms. Detection of the CYP3A5*3 genotype before the administration of TAC may provide some clinical value for optimizing the treatment of MN patients.</p></sec><sec><title>Systematic Review Registration:</title><p><ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://inplasy.com/">https://inplasy.com/</ext-link>, identifier [INPLASY202430083].</p></sec>