Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients

被引:1
|
作者
Rotarescu, Corina Andreea [1 ,2 ]
Maruntelu, Ion [1 ,2 ]
Rotarescu, Ion [3 ]
Constantinescu, Alexandra-Elena [1 ]
Constantinescu, Ileana [1 ,2 ,4 ]
机构
[1] Carol Davila Univ Med & Pharm, Dept Immunol & Transplant Immunol, 37 Dionisie Lupu St, Bucharest 020021, Romania
[2] Fundeni Clin Inst, Dept Immunogenet & Virol, 258 Fundeni Ave, Bucharest 022328, Romania
[3] Prof Dr CC Iliescu Emergency Inst Cardiovasc Dis, Dept Cardiovasc Surg, 258 Fundeni Ave, Bucharest 022328, Romania
[4] Acad Romanian Scientists AOSR, 3 Ilfov St, Bucharest 030167, Romania
关键词
kidney transplant; ABCB1; tacrolimus; haplotype; diplotype; P-GLYCOPROTEIN; TROUGH LEVELS; MDR1; PHARMACOKINETICS; CYP3A5; LIVER; RISK;
D O I
10.3390/ijms252010999
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1-14 days, 15-30 days, 31-60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (PFDR) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time.
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页数:11
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