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
  • [21] CYP3A5 and CYP3A4, but not ABCB1 polymorphisms affect tacrolimus dose-adjusted trough concentrations in kidney transplant recipients
    Kurzawski, Mateusz
    Dabrowska, Justyna
    Dziewanowski, Krzysztof
    Domanski, Leszek
    Peruzynska, Magdalena
    Drozdzik, Marek
    PHARMACOGENOMICS, 2014, 15 (02) : 179 - 188
  • [22] Tacrolimus trough levels in kidney transplant recipients
    Hwang, Young Hui
    Kim, Hyunjung
    Min, Kyungok
    Yang, Jaeseok
    BMC NEPHROLOGY, 2021, 22 (01)
  • [23] Computational validation of ABCB1 gene polymorphism and its effect on tacrolimus dose concentration/levels in renal transplant individuals of South India
    Mallina, Haritha
    Elumalai, Ramprasad
    Paul, Solomon F. D.
    Doss, C. George Priya
    Kumar, S. Udhaya
    Ramanathan, Gnanasambandan
    COMPUTERS IN BIOLOGY AND MEDICINE, 2021, 139
  • [24] Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients
    Crettol, Severine
    Venetz, Jean-Pierre
    Fontana, Massimiliano
    Aubert, John-David
    Ansermot, Nicolas
    Fathi, Marc
    Pascual, Manuel
    Eap, Chin B.
    PHARMACOGENETICS AND GENOMICS, 2008, 18 (04) : 307 - 315
  • [25] Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients
    Provenzani, Alessi
    Notarbartolo, Monica
    Labbozzetta, Manuela
    Poma, Paola
    Vizzini, Giovanni
    Salis, Paola
    Caccamo, Chiara
    Bertani, Tullio
    Palazzo, Ugo
    Polidori, Piera
    Gridelli, Bruno
    D'Alessandro, Natale
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2011, 28 (06) : 1093 - 1102
  • [26] Sequential analysis of tacrolimus dosing in adult lung transplant patients with ABCB1 haplotypes
    Zheng, HX
    Schuetz, E
    Zeevi, A
    Zhang, F
    McCurry, K
    Webber, S
    Iacono, A
    Lamba, J
    Burckart, GJ
    JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 45 (04) : 404 - 410
  • [27] Relationship of CYP3A5 genotype and ABCB1 diplotype to tacrolimus disposition in Brazilian kidney transplant patients
    Cusinato, Diego Alberto C.
    Lacchini, Riccardo
    Romao, Elen A.
    Moyses-Neto, Miguel
    Coelho, Eduardo B.
    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2014, 78 (02) : 364 - 372
  • [28] Sex Differences in Cyclosporine Pharmacokinetics and ABCB1 Gene Expression in Mononuclear Blood Cells in African American and Caucasian Renal Transplant Recipients
    Tornatore, Kathleen M.
    Brazeau, Daniel
    Dole, Kiran
    Danison, Ryan
    Wilding, Gregory
    Leca, Nicolae
    Gundroo, Aijaz
    Gillis, Kathryn
    Zack, Julia
    DiFrancesco, Robin
    Venuto, Rocco C.
    JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 53 (10) : 1039 - 1047
  • [29] Influence of ABCB1 gene polymorphism on concentration to dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients
    Azam, Fahad
    Khan, Moosa
    Khaliq, Tanwir
    Bhatti, Abu Bakar Hafeez
    PAKISTAN JOURNAL OF MEDICAL SCIENCES, 2021, 37 (03) : 689 - 694
  • [30] ABCB11 and ABCB1 gene polymorphisms impact on telaprevir pharmacokinetic at one month of therapy
    Cusato, Jessica
    Allegra, Sarah
    De Nicolo, Amedeo
    Boglione, Lucio
    Fatiguso, Giovanna
    Cariti, Giuseppe
    Ciancio, Alessia
    Smedile, Antonina
    Strona, Silvia
    Troshina, Giulia
    Rizzetto, Mario
    Di Perri, Giovanni
    D'Avolio, Antonio
    BIOMEDICINE & PHARMACOTHERAPY, 2015, 69 : 63 - 69