ABSTRACT: Transplanting of pancreatic grafts is an established treatment for diabetes mellitus. Polymorphisms in genes, coding for proteins involved in an immune response, may influence immunologic and nonimmunologic mechanisms that lead to allograft loss. Vitamin D receptor agonists have been shown to increase long-term allograft survival in humans.
Twenty-one pancreatic recipients transplanted in the Transplantation center of Shiraz University of Medical Sciences were selected and genotyped for the polymorphism of the vitamin D receptor genes (FokI), and the association of each genotype with acute rejection was evaluated. A control group of 100 unrelated otherwise healthy individuals, from the Iranian Blood Transfusion Organization were enrolled. The individuals were selected from Shiraz (a city located in Southern Iran), and the genotype frequency was compared with control group.
The overall prevalence acute rejection was 28% (6/21). In the genotype study, homozygous FF presented in 15 patients (71%), heterozygous Ff presented in 6 patients (29%), and no homozygous ff was identified. In the control group, there were 50% with FF, 48% with Ff, and 2% with the ff genotype identified. The only genotype that was detected in rejection group was FF, while the frequency of FF in the nonrejection group was 60%.
This study examined several patients to determine whether the vitamin D receptor (FokI) genotype is involved in acute allograft rejection and requires deeper investigation.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 04/2012; 10(5):428-32.
ABSTRACT: Liver transplant is an established treatment for end-stage liver failure. Vitamin D has been shown to exert multiple immunomodulatory effects, which act through its own receptor (vitamin D receptor). In the present study, the association between Iranian patients with liver transplant and the polymorphism of vitamin D receptor FokI T>C (rs10735810) was investigated.
The candidate gene locus was genotyped in 51 liver transplant recipients, and the association of each genotype with allograft acute rejection was evaluated.
In this study, we found no evidence to suggest that vitamin D receptor FokI polymorphism determines the incidence of acute rejection after liver transplant. The distribution of alleles was not different according to the underlying liver disease.
Larger epidemiologic studies are needed to elucidate the importance of vitamin D receptor gene polymorphism in transplant recipients.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 12/2010; 8(4):314-7.
ABSTRACT: Cytotoxic T-lymphocyte antigen 4 (CTLA4) has a critical role in the down-regulation of the immune response. We retrospectively examined the association between acute rejection and the single nucleotide polymorphism A/G in the CTLA-4 CT60 gene in liver transplant recipients.
Fifty-one liver transplant recipients with at least 3 months' follow-up were selected and genotyped for CTLA-4 CT60 polymorphism (HpyCH4 IV). The association of each genotype with allograft acute rejection was evaluated.
The mean age of patients was 27.9 +/- 15.17 years (minimum, 1 year, maximum, 55 years), with 39% male and 61% female. Overall, 17 recipients (33.3%) experienced acute rejection within the first 3 months after a liver transplant. In our study, 50% of the patients (n=26) have G/A , 31% (n=16) have A/A, and 17% have G/G genotypes (n=9). Distribution of alleles was not different according to underlying liver disease. There also was no difference in sex, age, and distributions of CTLA-4 CT60 alleles with acute rejection episodes.
CT60 A/G dimorphism within the 3'-UTR of CTLA4 gene does not influence acute rejection development in liver transplant. However, organ rejection is determined by a combination of several genetic traits rather than a single gene. Therefore, more studies with larger patient numbers are necessary to investigate the effect of combinations of genetic phenotypes involved in this process.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 09/2010; 8(3):210-3.
ABSTRACT: Hematopoietic stem-cell transplant is a curative therapy for several malignant and nonmalignant disorders. The purpose of this study was to investigate the association of serum levels of high-sensitivity C-reactive protein and procalcitonin with complications such as acute graft-versus-host disease, veno-occlusive disease, and infection after hematopoietic stem-cell transplant.
Serum high-sensitivity C-reactive protein and procalcitonin levels were sequentially measured with an enzyme-linked immunosorbent assay and a semiquantitative immunochromatographic assay in 35 patients who had undergone hematopoietic stem-cell transplant.
The high-sensitivity C-reactive protein serum level was increased in patients with acute graft-versus-host disease and in those with sepsis. Increased procalcitonin levels were associated only with bacterial infection. Only procalcitonin levels differentiated patients with infection from those with another transplant-related complication. Veno-occlusive disease did not alter C-reactive protein or procalcitonin levels.
Our results support theories that serum levels of high-sensitivity C-reactive protein and procalcitonin are biomarkers for transplantrelated complications such as graft-versus-host disease or infection and that the procalcitonin level can differentiate patients with infection from those with graft-versus-host disease.
Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation 07/2009; 7(2):115-8. · 0.81 Impact Factor
ABSTRACT: Methotrexate may be used as a prophylactic agent against graft-versus-host disease in hematopoietic cell transplant. The drug exerts its effect on folate metabolism; 5,10-methylenetetrahydrofolate reductase is a critical enzyme involved in this cycle and is related to the toxicity of methotrexate.
We examined the association of a single nucleotide polymorphism at position 677 in the 5,10-methylenetetrahydrofolate reductase gene and the clinical outcomes of patients treated with allogeneic hematopoietic cell transplant. Genotyping of 5,10-methylenetetrahydrofolate reductase was performed by polymerase chain reaction-restriction fragment length polymorphism on 30 patients receiving hematopoietic cell transplant and their HLA-matched related donors. Patients were given a short course of methotrexate as prophylaxis to prevent graft-versus-host disease.
Donors and recipients who carried a 677T allele showed mildly higher total bilirubin, aspartic transaminase, and alanine transaminase levels, but these increases above the normal values were not statistically significant (P > .05). The platelet recovery to 20 000/muL and granulocyte recovery to 500/muL were slower for patients who carried a 677T allele, but these correlations also were not statistically significant. The 5,10-methylenetetrahydrofolate reductase genotypes of neither the donors nor the recipients had any effect on the incidence of acute graft-versus-host disease.
No association was observed between the C677T polymorphism and the outcome parameters for any of the different genotypes studied here. Additional studies with larger samples are necessary to further elucidate the influence of 5,10- methylenetetrahydrofolate reductase genotyping on clinical outcomes of patients treated with hematopoietic cell transplant who receive methotrexate.
Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation 12/2007; 5(2):693-7. · 0.81 Impact Factor