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.
引用
收藏
页数:11
相关论文
共 50 条
  • [41] Contribution of ABCB1 gene polymorphisms to breast cancer cells response to chemotherapy
    Holysz, Hanna
    Rubis, Blazej
    MENOPAUSE REVIEW-PRZEGLAD MENOPAUZALNY, 2013, 12 (04): : 321 - 327
  • [42] The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients
    Haufroid, V
    Mourad, M
    Van Kerckhove, V
    Wawrzyniak, J
    De Meyer, M
    Eddour, DC
    Malaise, J
    Lison, D
    Squifflet, JP
    Wallemacq, P
    PHARMACOGENETICS, 2004, 14 (03): : 147 - 154
  • [43] Long-Term Influence of CYP3A5, CYP3A4, ABCB1, and NR1I2 Polymorphisms on Tacrolimus Concentration in Chinese Renal Transplant Recipients
    Liu, Fei
    Ou, Yang-Meng
    Yu, Ai-Rong
    Xiong, Lei
    Xin, Hua-Wen
    GENETIC TESTING AND MOLECULAR BIOMARKERS, 2017, 21 (11) : 663 - 673
  • [44] ABCB1 gene polymorphisms and violent suicide attempt among survivors
    Penas-Lledo, E.
    Guillaume, S.
    Delgado, A.
    Naranjo, M. E. G.
    Jaussent, I.
    LLerena, A.
    Courtet, P.
    JOURNAL OF PSYCHIATRIC RESEARCH, 2015, 61 : 52 - 56
  • [45] Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia
    Gregers, J.
    Green, H.
    Christensen, I. J.
    Dalhoff, K.
    Schroeder, H.
    Carlsen, N.
    Rosthoej, S.
    Lausen, B.
    Schmiegelow, K.
    Peterson, C.
    PHARMACOGENOMICS JOURNAL, 2015, 15 (04) : 372 - 379
  • [46] Association of ABCB1 gene polymorphisms and their haplotypes with response to antiepileptic drugs: a systematic review and meta-analysis
    Haerian, Batoul Sadat
    Lim, Kheng Seang
    Tan, Chong Tin
    Raymond, Azman Ali
    Mohamed, Zahurin
    PHARMACOGENOMICS, 2011, 12 (05) : 713 - 725
  • [47] Influence of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics/Pharmacodynamics of Tacrolimus in Pediatric Patients
    Yang, Mengjie
    Huan, Gui
    Wang, Mei
    CURRENT DRUG METABOLISM, 2018, 19 (14) : 1141 - 1151
  • [48] CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation
    Glowacki, Francois
    Lionet, Arnaud
    Buob, David
    Labalette, Myriam
    Allorge, Delphine
    Provot, Francois
    Hazzan, Marc
    Noel, Christian
    Broly, Franck
    Cauffiez, Christelle
    NEPHROLOGY DIALYSIS TRANSPLANTATION, 2011, 26 (09) : 3046 - 3050
  • [49] Impact of genetic polymorphisms on tacrolimus trough blood concentration in Chinese liver transplant recipients
    Maseko, Nicola
    Yang, Siyao
    Li, Chengcheng
    Zhang, Siqi
    Wang, Ruiying
    Zhang, Yawen
    Li, Chuanjiang
    Zhang, Chuanjie
    Li, Liang
    PHARMACOGENOMICS, 2023, 24 (04) : 207 - 217
  • [50] Impact of FOXP3 Polymorphisms on the Blood Level of Tacrolimus in Renal Transplant Recipients
    Ge, J.
    Wang, J.
    Zhao, H.
    Li, K.
    Jing, Y.
    Li, G.
    TRANSPLANTATION PROCEEDINGS, 2016, 48 (06) : 1962 - 1967