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. 2024 May 21:15:1385322.
doi: 10.3389/fphar.2024.1385322. eCollection 2024.

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

Xiaona Dai  1 , Fang Yuan  1 , Lan Chai  1
Affiliations

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

Xiaona Dai et al. Front Pharmacol. .

Abstract

Objective: 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).

Methods: 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.

Results: 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), p < 0.001] and 1-6 months [WMD = -0.63, 95% CI (-0.98, -0.27), p < 0.001]; however, they were not statistically significant at ≥6 months (p = 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), p < 0.001], 1-6 months [SMD = -2.25, 95% CI (-2.71, -1.79), p < 0.001], and ≥6 months [SMD = -2.36, 95% CI (-2.86, -1.86), p < 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 (p > 0.05).

Conclusion: 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.

Systematic review registration: https://inplasy.com/, identifier [INPLASY202430083].

Keywords: CYP3A5; gene polymorphism; membranous nephropathy; meta-analysis; tacrolimus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of the studies included in this meta-analysis.
FIGURE 2
FIGURE 2
Forest plot of a meta-analysis of the difference in tacrolimus blood trough concentration between AA + AG and GG genotypes. The studies were divided into subgroups for analysis according to the duration of tacrolimus administration as ≤1 month, 1–6 months, and ≥6 months. WMD, weighted mean difference; CI, confidence interval.
FIGURE 3
FIGURE 3
Forest plot of the difference in tacrolimus C0/D between AA + AG and GG genotypes in MN patients. The studies were divided into subgroups for analysis according to the duration of tacrolimus administration as ≤1 month, 1–6 months, and ≥6 months. SMD, standard mean difference; CI, confidence interval.
FIGURE 4
FIGURE 4
Forest plot of the relationship between CYP3A5*3 gene polymorphisms and the effectiveness of tacrolimus in treating MN patients. The studies were divided into subgroups for analysis according to the duration of tacrolimus administration as 3 months, 6 months, and 12 months. OR, odds ratio; CI, confidence interval.
FIGURE 5
FIGURE 5
Funnel plot of the publication bias assessment and Begg’s test.
See this image and copyright information in PMC

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