Dataset Information

CTLA4 polymorphisms and de novo malignancy risk after renal transplantation in Chinese recipients.

ABSTRACT: Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4) play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of five CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with de novo malignancy in 1463 Chinese renal transplantation (RT) recipients who underwent a 192-month follow-up. Multivariate analyses revealed that recipient rs231775 genotype is significantly associated with tumorigenesis (P = 0.012). Multiplicative interaction between rs231775 AA and possible risk factors of malignancy revealed two significant results: rs231775 AA?×?primary diseases and rs231775 AA?×?number of HLA-mismatch. The frequency of haplotype TACAG was significantly higher in the tumor group (17.07%) than that in the nontumor group (1.53%). In addition, aristolochic acid nephropathy (P = 0.003) and the time of discovery of tumor (P = 0.000) also were independently associated with tumorigenesis. Our data show that the CTLA4 genotype rs231775 AA may be one of risk factors for the development of malignancy and haplotype TACAG was susceptible haplotype in Chinese kidney transplant recipients.

SUBMITTER: Guo YF

PROVIDER: S-EPMC4312582 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CTLA4 polymorphisms and de novo malignancy risk after renal transplantation in Chinese recipients.

Guo Yi-feng YF Qiu Jian-xin JX Guo Fang F Liu Yong Y Shang Ming-hua MH

BioMed research international 20150115

Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4) play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of five CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with de novo malignancy in 1463 Chinese renal transplantation (RT) recipients who underwent a 192-month follow-up. Multivariate analyses revealed that reci ...[more]

PMID: 25667935

Similar Datasets

Project description:BACKGROUND: Immunosuppressive 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. METHODS: In this study, the risk of infection according to CTLA4 SNPs was investigated in 304 patients who received kidney graft transplants between 2008 and 2012. RESULTS: The 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. CONCLUSIONS: The 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.

Project description:BACKGROUND/OBJECTIVE:RAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients. METHODS:Six single nucleotide polymorphisms (SNPs) of RAC1 gene, including rs836488 T>C, rs702482 A>T, rs10951982 G>A, rs702483 A>G, rs6954996 G>A, and rs9374 G>A, were genotyped in 300 renal transplant recipients (cases) and 998 healthy Chinese subjects (controls) by using TaqMan SNP genotyping assay. Allele, genotype, and haplotype frequencies of the six SNPs were compared between cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models to evaluate the associations of the six SNPs with ESRD risk. RESULTS:The genotype distributions for the six SNPs in controls were consistent with Hardy-Weinberg equilibrium (P > 0.05). Association analysis revealed that three SNPs were significantly associated with ESRD risk. Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model (minor allele homozygotes versus major allele homozygotes); specifically, the frequencies of the minor allele homozygotes and the minor allele for the three SNPs were higher in the cases than in the controls. In addition, these three SNPs also had associations with increased ESRD risk under the additive model (P < 0.05), and positive associations were also found for the rs836488 in the dominant model (P < 0.05) and for the rs702483 in the recessive model (P < 0.05). All these associations were independent of confounding factors. The other three SNPs (rs10951982, rs6954996, and rs9374), in all comparison models, were not associated with ESRD risk (P > 0.05). In haplotype analysis, carriers with "C-T-G-G-G-G" haplotype had a significantly higher risk of ESRD compared with the most common haplotype "T-A-G-A-G-G" (P = 0.011, OR = 1.46, 95% CI = 1.09-1.94). CONCLUSION:This study suggested that polymorphisms of RAC1 gene might influence the susceptibility to ESRD in Chinese Han population. Further studies are necessary to confirm our findings.

Project description:Background: Despite significant improvements in short-term kidney transplant survival, comparable increases in 5 and 10-year outcomes have not been achieved. Chronic allograft nephropathy (CAN) is a major cause of late graft loss. Toxic nephropathy and inadequate long-term immunosuppression are possible factors. We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure, and gene expression. Methods: Sixty-one kidney recipients received mycophenolate mofetil (MMF), and prednisone (P). Randomized patients received concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Findings: Comparing sirolimus/MMF/P to cyclosporine/MMF/P at two years, there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dl; p=0.008), significantly higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 cc/min; p=0.008), iothalamate GFR (60.6 vs. 49.2 cc/min; p= 0.018), and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p=0.013). Regression analysis of calculated GFR’s from 1 to 36 months yielded a positive slope for sirolimus of 3.36 ml/min/year, and a negative slope for cyclosporine of –1.58 ml/min/year (p=0.008). Gene expression profiles of kidney biopsies with higher Banff CAN scores confirmed significant up regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. Interpretation: At two years the sirolimus-treated patients have better renal transplant function, a diminished prevalence of CAN, and down regulated expression of genes responsible for the progression of CAN. All may provide for an alternative natural history with improved graft survival. Keywords = Cyclosporine Keywords = Sirolimus Keywords = Transplantation Keywords = DNA microarrays Keywords = calcineurin inhibitors Keywords: parallel sample. This dataset is part of the TransQST collection.

Dataset Information

CTLA4 polymorphisms and de novo malignancy risk after renal transplantation in Chinese recipients.

Publications

CTLA4 polymorphisms and de novo malignancy risk after renal transplantation in Chinese recipients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets