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Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients

ABSTRACT: Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients

PROVIDER: PRJNA486228 | ENA |

REPOSITORIES: ENA

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Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients

Project description:Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients

| PRJNA486227 | ENA

Distinct peripheral blood molecular signature emerges with successful tacrolimus withdraw in kidney transplant recipients

Project description:Tacrolimus (Tac) is an effective anti-rejection agent in kidney transplantation, but its off-target effects make withdrawal desirable. While studies indicate that Tac can be safely withdrawn in a subset of kidney transplant recipients, immune mechanisms that underlie successful vs. unsuccessful Tac removal are unknown. We performed microarray analyses of PBMC RNA from subjects enrolled in the Clinical Trials in Organ Transplantation-09 study in which stable kidney transplant recipients were randomized to Tac withdrawal or maintenance of standard immunosuppression beginning 6-mo post-transplant. Eight of 14 subjects attempted but failed withdrawal, while six developed stable graft function for ≥2 years on mycophenolate mofetil plus prednisone. Whereas failed withdrawal upregulated immune activation genes, successful Tac withdrawal was associated with a distinct, T cell-specific, downregulatory, and pro-apoptotic gene program. Functional analyses suggested stronger donor-reactive immunity in subjects who failed withdrawal without evidence of regulatory T cell dysfunction. Together, our data suggest that successful Tac withdrawal can unleash an active, protective pro-apoptotic T cell program, and provide the foundation for developing strategies to promote this protective immunological phenotype in kidney transplant recipients.

2020-02-18 | GSE145408 | GEO

Cellular and Molecular Immune Profiles in Renal Transplant Recipients after Conversion from Tacrolimus to Sirolimus

Project description:Tacrolimus and Sirolimus are commonly used to maintain immunosuppression in kidney transplantation. However, their effects on immune cells and allograft molecular profiles have not been elucidated. Here we characterized the effects of Tacrolimus to Sirolimus conversion on frequency and function of T cells, and on graft molecular profiles. Samples from 30 renal transplant recipients in a randomized trial of late Sirolimus conversion (n=18) vs. Tacrolimus maintenance (n=12) were utilized. Peripheral blood was collected at 0- 6- 12 and 24-months post-randomization. This dataset only contains the 18 arrays corresponding to patients treated with Sirolimus.

2014-09-17 | E-GEOD-55998 | biostudies-arrayexpress

Kidney transplant recipients

Project description:Kidney transplant recipients

| PRJNA1054489 | ENA

Affymetrix SNP array data for kidney transplant samples

Project description:Tacrolimus (TAC) is an immunosuppressant widely used in kidney transplantation. TAC displays considerable inter-individual variability in pharmacokinetics (PK). Genetic and clinical factors play important roles in TAC PK. To define genetic factors associated with tacrolimus blood trough concentration, we performed a genome-wide association study of renal transplant samples from 251 Chinese renal transplant recipients. We identified 23 single nucleotide polymorphisms (SNPs) related to TAC PK variability. All 23 genome-wide significant SNPs (p<5E-8) were located on chromosome 7, including rs776746. These findings suggest that these SNPs may be associated with the unexlained TAC PK variability in renal transplant recipients and require further investigation.

2022-02-24 | GSE196772 | GEO

Distinct peripheral blood molecular signature emerges with successful tacrolimus withdraw in kidney transplant recipients

Project description:Distinct peripheral blood molecular signature emerges with successful tacrolimus withdraw in kidney transplant recipients

| PRJNA607101 | ENA

NGS in hematopoietic cell transplant recipients

Project description:Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pre-transplant genetic susceptibility is evident in adult TA-TMA patients at the level of TMA-associated variants and further investigated the association of genetic variants with clinical outcomes. We studied 30 patients with TA-TMA at a median of 73 (9-540) post-transplant days, donors of 18/30 patients and 30 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pre-transplant peripheral blood was analyzed by targeted next generation sequencing for complement regulatory genes and ADAMTS13. Donors presented significantly lower frequency of rare variants (p=0.049) and variants in exonic/splicing/UTR regions (p=0.025), compared to TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in ADAMTS13 (p=0.001), CD46 (p=0.002), CFH (p=0.010) and CFI (p=0.031). Pathogenic variants were found in ADAMTS13, CFH, CFI and CFB, while homozygous pathogenic variants in ADAMTS13 and CFB were evident in only 4 TA-TMA patients (p=0.038). Patients refractory to conventional treatment (70%) were significantly (p=0.045) enriched for variants in exonic/splicing/UTR regions compared to responders. Nineteen of 30 patients (63%) succumbed to transplant-related mortality, which was also associated with significantly (p=0.012) increased frequency of variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pre-transplant genomic screening may be useful to intensify monitoring and early intervention in high-risk patients.

2019-04-18 | E-MTAB-7848 | biostudies-arrayexpress

Biomarkers in Transplant Recipients

Project description:Biomarkers in Transplant Recipients

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DNA methylation profiling of kidney transplant recipients

Project description:DNA methylation profiling of kidney transplant recipients

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Adipose tissue gene expression associated with weight gain in kidney transplant recipients

Project description:The aim of this study was to investigate the association of gene expression profiles in subcutaneous adipose tissue with percent of total body weight change in 26 kidney transplant recipients. Using multivariate linear regression analysis controlled for race and gender, expression levels of 1553 genes were significantly (p<0.05) associated with weight change. A secondary data analysis was done on a subgroup (n=26) of existing clinical and gene expression data from a larger prospective longitudinal study examining factors contributing to weight gain in transplant recipients.

2013-10-04 | E-GEOD-33070 | biostudies-arrayexpress

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