Dataset Information

Impact of genetic polymorphisms at the promoter area of IL-10 gene on tacrolimus level in Jordanian renal transplantation recipients.

ABSTRACT:

Background

Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients.

Methods

Blood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients.

Results

Genotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation 88.2±32.1 vs. 117.5±22.5 ng/mL per mg/kg/day, p=0.04 .

Conclusions

Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the first month post-transplantation.

SUBMITTER: Khaleel B

PROVIDER: S-EPMC9375538 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of genetic polymorphisms at the promoter area of IL-10 gene on tacrolimus level in Jordanian renal transplantation recipients.

Khaleel Bara'ah B Yousef Al-Motassem AM Al-Zoubi Mazhar Salim MS Al-Ulemat Muhammad M Masadeh Ahmad A AA Abuhaliema Ali A Al-Batayneh Khalid M KM Al-Trad Bahaa B

Journal of medical biochemistry 20220701 3

<h4>Background</h4>Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the D ...[more]

PMID: 36042898

Similar Datasets

Project description:BackgroundTacrolimus is one of the most commonly used basic immunosuppressants nowadays, but the high variability of tacrolimus blood concentration often leads to kidney transplant recipients frequently experiencing drug concentrations above or below the target concentration, resulting in renal toxicity or rejection of the transplanted kidney. The aim of this study is to explore the correlation of renal function with intra-patient variability (IPV) of tacrolimus blood concentration among recipients of renal transplants at 1-, 3-, 5-, and 10-year post-transplantation.MethodsRecipients of renal transplants who were treated with tacrolimus for immunosuppression at the Shanghai General Hospital between January 2001 and December 2009, and followed up until 2019 were included in this retrospective study. Demographic characteristics and laboratory investigation results at their 1-, 3-, 5-, and 10-year follow-up visits were collected from their hospital medical records. Patients were divided into a low or high IPV group based on the IPV of their tacrolimus concentrations.ResultsA total of 167 kidney transplant recipients were included in the study. At the 3-year follow-up visit, patients in the low IPV group had significantly lower blood urea nitrogen (BUN) (6.3±1.8 vs. 8.2±6.2 µmol/L, P=0.04), serum creatinine (Scr) (88.8±23.6 vs. 104.8±39.6 µmol/L, P=0.009), and blood uric acid (UA) (329.1±80.2 vs. 375.9±95.1 µmol/L, P=0.004), as well as significantly higher estimated glomerular filtration rate (eGFR) values than patients in the high IPV group. Blood UA levels were significantly lower in patients in the low IPV group than the high IPV group at the 10-year follow-up (362.7±92.6 vs. 398.5±105.2 µmol/L, P=0.042). There was no significant difference between the low and high IPV groups with respect to BUN, Scr, UA, or eGFR at the 1- and 5-year follow-up.ConclusionsRecipients of renal transplants with lower IPV in tacrolimus concentration appeared to have better renal function over time. Controlling IPV may contribute to improved renal outcomes post-transplantation.

Project description:BackgroundImmunosuppressive therapy is usually administered following renal transplantation to protect the graft from rejection. However, this often causes complications such as infections to occur. Single nucleotide polymorphisms (SNPs) within the CTLA4 gene, such as -1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), can affect graft rejection and the long-term clinical outcome of organ transplantation. The role of CTLA4 SNPs in T cell-mediated immunity in renal transplantation and association with infection after transplantation is unknown.MethodsIn this study, the risk of infection according to CTLA4 SNPs was investigated in 304 patients who received kidney graft transplants between 2008 and 2012.ResultsThe frequency of the rs4553808 GG genotype was significantly higher in recipients with viral infection (14.89%) than in those without infections (3.50%) (Bonferroni-adjusted p = 0.005). A significant difference (p = 0.001) in patients with the rs4553808 GG genotype from those with the AA+AG genotypes was found in the viral cohort using the log-rank test. A significant association was found between the rs4553808 genotype and onset of viral infection in transplant recipients (p = 0.001). The frequencies of the CGTAG and CGCAG haplotypes were significantly higher in the viral infection group (9.6% and 5.3%) than in the non-viral infection group (3.8% and 1.4%) (p = 0.0149 and p = 0.0111). No association between any CTLA4 SNP and bacterial infection was found. Multivariate analyses revealed that one risk factor, the use of antibody induction therapy (p = 0.007), was associated with bacterial infection, and two risk factors, antibody use (p = 0.015) and recipient rs4553808 genotype (p = 0.001), were associated with viral infection.ConclusionsThe rs4553808 GG genotype may be a risk factor for viral infection in kidney transplantation. The CTLA4 haplotypes CGTAG and CGCAG were partially associated with the development of viral infection in Chinese kidney transplant recipients.

Dataset Information

Impact of genetic polymorphisms at the promoter area of IL-10 gene on tacrolimus level in Jordanian renal transplantation recipients.

Background

Methods

Results

Conclusions

Publications

Impact of genetic polymorphisms at the promoter area of IL-10 gene on tacrolimus level in Jordanian renal transplantation recipients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets