Association of vitamin D binding protein polymorphism with long-term kidney allograft survival in Hispanic kidney transplant recipients

Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP G>T polymorphism (rs4588) and two haplotypes (GTCG and ACCA) of VDR appear to be associated with renal allograft outcomes among Hispanic allograft recipients.     

Influence of recipient and donor IL-10, TNFA and INFG genotypes on the incidence of acute renal allograft rejection

Objective Transplantation of renal grafts is an established treatment for renal failure in a variety of medical conditions. Acute allograft rejection remains an important cause of morbidity after kidney transplantation, and has been shown to be a crucial determinant of long-term graft function. Although rejection is mediated by recipient lymphocytes, both donor and recipient factors contribute to the local environment that influences the severity of rejection response. Because cytokines are the main components of immune responses, we evaluate single nucleotide polymorphisms (SNP) of several cytokine genes that may influence the production of a given cytokine and therefore the features of immune reactions. Material and Methods The aim of this study was to determine the impact of the cytokine gene polymorphism of pro and anti-inflammatory cytokines on the development of acute allograft rejection, which could be used in pretransplant patient assessment. Three SNPs including IL-10 (−1082 G/A), TNFA (−308 G/A), and INFG (+874 T/A) were analyzed in 46 patients with acute allograft rejection, 54 patients with stable graft function and their kidney donors by PCR-ARMS method. Results We are unable to find statistically significant association between any of the studies polymorphisms and clinical outcomes. Conclusion We have found no evidence to suggest that either recipient or donor cytokines polymorphisms determine the incidence of acute rejection after renal transplantation. Our observation, however, is based on few cases, and this may mask a possible favorable effect. It is recommended that several functionally related genes should be tested in similar studies, since this approach has a higher chance to detect genetic risk factors than the screening of single genetic variants.     

The effect of chemokine receptor gene polymorphisms (CCR2V64I,CCR5-59029G>A and CCR5Δ32) on renal allograft survival in Pakistani transplant patients

Background

Gene polymorphisms of the chemokine receptors CCR2 and CCR5 (CCR2V64I, CCR5-59029G>A and CCR5Δ32) have been shown to be associated with renal allograft rejection. The aim of this study was to investigate the association of these polymorphisms with allograft rejection among Pakistani transplant patients.

Method

A total of 606 renal transplant patients and an equal number of their donors were included in this study. DNA samples were used to amplify polymorphic regions of CCR2V64I, CCR5-59029G>A and CCR5Δ32 by polymerase chain reaction using sequence specific primers. The amplified products of CCRV64I and CCR5-59029G>A were digested with restriction enzymes (BsaB1 and Bsp12861) respectively. The CCR5Δ32 genotypes were determined by sizing the PCR amplicons. The association of these polymorphisms with the biopsy proven rejection and other clinical parameters was evaluated using the statistical software SPSS v.17.

Results

In this study, the G/G genotype of CCR2V64I was associated with a high frequency of allograft rejection (p = 0.009; OR = 2.14; 95% CI = 1.2–3.7). Rejection episode(s) in the GA + AA genotypes were found to be significantly lower as compared to the GG genotype (p = 0.009; OR = 0.4; 95% CI = 0.2–0.8). The Kaplan–Meier curve also indicated a reduced overall allograft survival for patients with the G/G genotype of CCR2V64I (59.2 ± 1.4 weeks, log p = 0.008). There was a significant association with rejection by female donors possessing the CCR2 GG genotype (p = 0.02; OR = 2.6; CI = 1.1–6.3) and male donors with the CCR5-59029 GG genotype (p = 0.004; OR = 1.7; CI = 1.03–3.01).

Conclusion

This study shows an association of the CCR2V64I (G/G) genotype with renal allograft rejection. However, no such association was found for the CCR5 gene polymorphisms. Therapeutic interventions such as blocking the CCR2 receptor (especially G polymorphism) may yield better survival of renal allograft in this patient group. Further, chemokine receptors may be added to the spectrum of the immunogenetic factors that are known to be associated with renal allograft rejection.     

Characterization of acute renal allograft rejection by proteomic analysis of renal tissue in rat

Rapid and reliable biomarkers of renal allograft rejection have not been available. This study aimed to investigate biomarkers in renal allograft tissue using proteomic analysis. Orthotopic kidney transplantations were performed using Fisher (F344) or Lewis rats as donors and Lewis rats as recipients. Syngenic control group (Group I) constituted F344-to-F344 orthotopic kidney allo-transplantations (n = 8); and allogenic group (Group II) consisted of F344-to-Lewis orthotopic kidney allo-transplantations (n = 8). Renal tissues were harvested 7 days after transplantation. Samples were analyzed using 2-D electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry. 6 differentially expressed proteins were identified between allogenic group and syngenic control group. A rat model of acute renal allograft rejection was successfully set up. Differentially expressed proteins in renal allograft tissue of rat were detected using proteomic analysis and might serve as novel diagnostic and therapeutic targets in human. Quantitative proteomics, using MALDL-TOF-MS methodology has the potential to provide a profiling and a deeper understanding of acute renal rejection.     

Genetic control of rat heart allograft rejection: effect of different MHC and non-MHC incompatibilities

We investigated the genetic control of heterotopic heart allograft rejection using a family of standard inbred, major histocompatibility complex (MHC)-congenic, and intra-MHC recombinant rat strains. Gene products of the various regions within the rat MHC differed markedly in their capacity to induce rejection. Isolated incompatibility at class I antigens encoded by theRT1. A andRT1. C regions failed to induce rejection within the observation period of 100 days, whereas class II antigens encoded by theRT1.B/D region provoked rapid rejection within 10 days. By comparison of the rejection times of isolated and combined incompatibilities a number of functional interactions could be demonstrated between individual MHC regions which either prolonged or shortened allograft survival. In contrast to rapid rejection of MHC-mismatched heart allografts, differences at non-MHC histocompatibility antigens were associated with graft survival beyond 100 days, although chronic rejection of variable severity was detected histologically. Disparity at non-MHC plus class I antigens, however, provoked acute heart allograft rejection.     

Association of common variants of vascular endothelial growth factor and interleukin-18 genes with allograft survival in renal transplant recipients of North India

Increased vascular endothelial growth factor (VEGF) production promotes enhanced endothelial permeability, enhanced leukocyte migration into the allograft, thereby leading to a clinically recognized rejection episode. Interleukin-18 (IL-18), a potent proinflammatory cytokine, may also be involved in mechanisms of kidney allograft rejection. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in VEGF (2578C>A, 1154A>G) and IL-18 (607C>A, 137G>C) genes with risk of allograft rejection in renal transplant recipients of North India. Two hundred renal transplant recipients, 150 matched recipients-donors, and 200 unrelated healthy individuals were genotyped by amplification refractory mutation specific polymerase chain reaction and by polymerase chain reaction-restriction fragment length polymorphism. Variant allele VEGF 1154A>G (p?=?0.56; odds ratio [OR]?=?1.32) and variant allele (p?=?0.004, OR?=?1.54) and variant genotype (p?=?0.007, OR?=?3.26) of IL-18 607C>A, GC of IL-18 137G>C (p?=?0.043, OR?=?0.63) were significantly different in healthy individuals as compared with the patients with renal transplant. When 114 nonrejectors were compared with 36 rejectors (150 recipients) for association with allograft rejection, significant association was observed in heterozygous genotype of VEGF 2578C>A (p?=?0.033), VEGF 1154A>G (p?=?0.024). In IL-18 137G>C, CC genotype, C allele showed protective association with allograft rejection. Kaplan-Meier analysis indicated a higher mean time for first rejection episode in CA genotype carriers (31 months) as compared with AA (29 months) for VEGF 2578C>A (log p?=?0.035). In VEGF, the haplotypes A-A and A-G (2578-1154) were associated with reduced risk and in IL-18 607A-137G, they were associated with high risk for allograft rejection. This observation suggests these polymorphisms are an ideal marker for prediction of pretransplant allograft outcome.     

Involvement of interaction between viral VP466 and host tropomyosin proteins in virus infection in shrimp

The C3 component of complement has different roles in kidney disease and its local production in donor kidney may affect allograft function and rejection after organ transplantation. A single base substitution in c3 gene (rs2230199), defines two common allelic variants with different mobility on gel electrophoresis: S (Slow) and F (Fast). In order to evaluate the effect of this polymorphism on acute renal allograft rejection, one hundred samples of donor and recipients were collected and genotyping was done by PCR-RFLP method. The allelic frequencies were: C3S=0.791, C3F=0.209. There was no significant association between recipient's genotype and acute rejection (p value<0.05). No correlation between donor genotype and acute rejection was also present. Patients were divided into four groups, according to the recipient and donor genotypes: SS recipients and FS or FF donor, SS recipient and donor, FF or FS recipient and SS donor and FS or FF recipient and donor. There was no significant difference in rate of acute rejection between groups. Although the results didn't find any association between C3 complement polymorphisms and acute allograft rejection, there was no acute rejection in FS or FF donors and SS recipient group.     

Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection

Background

The association of complement with the progression of acute T cell mediated rejection (ATCMR) is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs) in acute T-cell mediated rejection using rat and human renal allografts.

Methods

We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR) and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP) by immunohistochemical staining in human renal grafts and their clinical course.

Results

qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry), was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.

Conclusions

We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.     

Genetic predisposition of donors affects the allograft outcome in kidney transplantation; polymorphisms of stromal-derived factor-1 and CXC receptor 4

Genetic interaction between donor and recipient may dictate the impending responses after transplantation. In this study, we evaluated the role of the genetic predispositions of stromal-derived factor-1 (SDF1) [rs1801157 (G>A)] and CXC receptor 4 (CXCR4) [rs2228014 (C>T)] on renal allograft outcomes. A total of 335 pairs of recipients and donors were enrolled. Biopsy-proven acute rejection (BPAR) and long-term graft survival were traced. Despite similar allele frequencies between donors and recipients, minor allele of SDF1 rs1801157 (GA+AA) from donor, not from recipients, has a protective effect on the development of BPAR compared to wild type donor (GG) (P = 0.005). Adjustment for multiple covariates did not affect this result (odds ratio 0.39, 95% C.I 0.20–0.76, P = 0.006). CXCR4 rs2228014 polymorphisms from donor or recipient did not affect the incidence of acute rejection. SDF1 was differentially expressed in renal tubular epithelium with acute rejection according to genetic variations of donor rs1801157 showing higher expressions in the grafts from GG donors. Contrary to the development of BPAR, the presence of minor allele rs1801157 A, especially homozygocity, predisposed poor graft survival (P = 0.001). This association was significant after adjusting for several risk factors (hazard ratio 3.01; 95% C.I = 1.19–7.60; P = 0.020). The allelic variation of recipients, however, was not associated with graft loss. A donor-derived genetic polymorphism of SDF1 has influenced the graft outcome. Thus, the genetic predisposition of donor should be carefully considered in transplantation.     

Role of nonclassical class I genes of the chicken major histocompatibility complex Rfp-Y locus in transplantation immunity

The chicken major histocompatibility complex (MHC) genes are organized into two genetically independent clusters which both possess class I and class II genes: the classical B complex and the Restriction fragment pattern-Y (Rfp-Y) complex. In this study, we have examined the role of Rfp-Y genes in transplantation immunity. For this we used three sublines, B19H1, B19H2 and B19H3, derived from a line fixed for B19. Southern blots, PCR-SSCP assays using primers specific for Rfp-Y genes, and Rfp-Y class I allele-specific sequencing show that the polymorphisms observed in B19H1, B19H2 and B19H3 are due to the presence of three different Rfp-Y haplotypes. The Rfp-Y class I (YF) alleles in these three haplotypes are highly polymorphic, and RT-PCR shows that at least two YF loci are expressed in each subline. The three sublines show Rfp-Y-directed alloreactivity in that Rfp-Y-incompatible skin grafts are rejected within 15 days, a rate intermediate between that seen in B-incompatible rejection (7 days) and that observed for grafts within the sublines (20 days). We conclude that Rfp-Y has an intermediate role in allograft rejection, likely to be attributable to polymorphism at the class I loci within this region.The sequence data reported are available in the GenBank database under the accession numbers AY257165 (YFVw*15), AY257166 (YFVw*16), AY257167 (YFVIw*15), AY257168 (YFVIw*17), AY257169 (YFw*16), and AY257170 (YFw*17)     

Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women

We examined whether polymorphisms of the vitamin D receptor (VDR) gene was associated with individual risk of hand osteoarthritis (OA). Radiographs of both hands of 295 dentists and of 248 teachers were examined and classified for the presence of OA using reference images. The VDR ApaI and TaqI genotypes were determined by PCR-based methods. No association was observed between the VDR polymorphisms and the odds of overall hand OA. However, the carriers of the VDR t allele or At haplotype were at almost half the odds of symmetrical hand OA (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38–0.94 and OR = 0.59, 95% CI = 0.38–0.93, respectively) compared with the carriers of the T allele and of the non-At haplotype, respectively. Increased odds of this disease, on the contrary, was observed for women with two copies of the VDR a allele (OR = 1.93, 95% CI = 1.99–3.70) compared with women with the AA genotype. Conversely, the VDR a allele carriage was associated with a tendency of lowered odds of osteophyte (OR = 0.51, 95% CI = 0.25–1.03). When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08–0.91) of osteophyte compared with the AAtt joint genotype. As a novel finding we observed a joint effect of a low calcium intake and VDR polymorphisms on symmetrical OA; the OR was 2.64 (95% CI = 1.29–5.40) for carriers of the aT haplotype with low daily calcium intake compared with non-carriers of the haplotype with high daily calcium intake. Our results suggest that VDR gene polymorphisms play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake.     

Influence of GSTO2 (N142D) genetic polymorphism on acute renal rejection

Acute renal allograft rejection remains an important problem following kidney transplantation. Several immunological and non-immunological factors intervene in renal graft rejection. Glutathione S-transferase super family is one of the important enzymes for biotransformation of both exogenous and endogenous xenobiotic compounds such as immunosuppressive drugs. The new class of this family is omega that includes two subunits GSTO1 and GSTO2. In this study 282 samples were collected from renal recipients of Namazi hospital in Shiraz-Iran during 2007–2010 years. Also 300 healthy samples as control group were collected from Shiraz population, included in our study. The primary outcome of this study was defined as biopsy-proven acute rejection during 1 year of renal transplantation. We applied polymerase chain reaction–restriction fragment length polymorphism method for determination of GSTO2 N142D polymorphism. Our result showed no significant association between GSTO2 polymorphism and acute rejection. Also this genetic variant has no significant effect with the risk of end stage renal disease. Cadaveric donor type for acute rejection significantly differed between acute rejection and non acute rejection patients (P = 0.004). The combination effect of donor type and GSTO2 polymorphism indicates DD genotype with cadaver donor type increase risk of acute rejection (OR = 3.82, 95 % CI 1.80–12.37, P = 0.02).     

Evaluation of <Emphasis Type="Italic">ERα</Emphasis> and <Emphasis Type="Italic">VDR</Emphasis> gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women

It has been suggested that the estrogen receptor alpha (ERα) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERα PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERα (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERα PvuII “PP” and ERα XbaI “XX” genotypes than in those with “Pp/pp” genotypes and “xx” genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI “FF” genotype had lower BMD values of femoral neck and total hip compared to those with “Ff” genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI “FF” genotypes, BMI ≤ 27.5, age ≥ 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERα PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women.     

Donor–Recipient Sex Mismatch in Kidney Transplantation

BackgroundThe lack of reliable human proxies for minor (ie, non-HLA) histocompatibility loci hampers the ability to leverage these factors toward improving transplant outcomes. Despite conflicting reports of the effect of donor–recipient sex mismatch on renal allografts, the association between acute rejection of renal allografts and the development of human alloantibodies to the male H-Y antigen suggested to us that donor–recipient sex mismatch deserved re-evaluation.ObjectiveTo evaluate whether the relationships between donor sex and allograft failure differed by recipient sex.MethodsWe studied recipients of deceased-donor (n = 125,369) and living-donor (n = 63,139) transplants in the United States Renal Data System. Using Cox proportional hazards models stratified by donor type, we estimated the association between donor–recipient sex mismatch and death-censored allograft failure with adjustment for known risk factors, with and without the use of multiple imputation methods to account for potential bias and/or loss of efficiency due to missing data.ResultsThe advantage afforded by male donor kidneys was more pronounced among male than among female recipients (8% vs 2% relative risk reduction; interaction P < 0.01). This difference is of the order of magnitude of several other risk factors affecting donor selection decisions.ConclusionsDonor–recipient sex mismatch affects renal allograft survival in a direction consistent with immune responses to sexually determined minor histocompatibility antigens. Our study provides a paradigm for clinical detection of markers for minor histocompatibility loci.     

Association between IL-4 polymorphism and acute rejection of solid organ allograft: A meta-analysis

Background

Cytokines have been implicated in the acute rejection of solid organ transplantation. Many studies have investigated the association between recipient or donor IL-4 polymorphism and acute rejection, with different studies reporting inconclusive results.

Methods

We searched PUBMED and EMBASE until June 2012 to identify eligible studies investigating the association between IL-4 polymorphism with acute rejection after solid organ transplantation. Statistical analysis was performed using STATA10.0.

Results

A total of 12 studies were included. Pooled ORs suggested 1) no significant association was detected between recipient or donor IL-4 − 590C/T polymorphism and acute rejection of solid allograft; 2) no significant association was detected between recipient IL-4 − 33C/T polymorphism and acute rejection of solid allograft; 3) when stratified by transplantation type, IL-4 − 590C/T polymorphism was associated with acute rejection of liver transplantation (T/T + C/T vs. C/C: OR = 0.36, 95%CI = 0.14–0.90); 4) significantly decreased risk of acute rejection was detected in recipient IL-4 − 590*T-negative/donor T-positive genotype pairs than all other recipient–donor IL-4 − 590T/C pairs (OR = 0.14, 95%CI = 0.03–0.66).

Conclusions

Our meta-analysis suggested that recipient IL-4 − 590C/T polymorphism was associated with acute rejection of liver transplantation, but nor renal or heart transplantation. It was also suggested that combined recipient IL-4 − 590*T-negative/donor T-positive genotype may suffer decreased risk of acute rejection of solid allograft. Further well-designed studies with larger sample size were required to verify our findings, with focus on the association of IL-4 polymorphism with acute rejection in patients with liver transplantation and studies investigating combined recipient–donor genotype.     

The contribution of SIPA1 and RRP1B germline polymorphisms to breast cancer phenotype,lymph node status and survival in a group of Lithuanian young breast cancer patients

The germline polymorphisms in signal-inducing proliferation-associated protein 1 (SIPA1) and ribosomal RNR processing 1B (RRP1B) might be involved in breast cancer metastasis. The aim of this study was to analyze how SIPA1 and RRP1B polymorphisms contribute to breast cancer phenotype, lymph node status and survival. A group of 100 young, I–II stage breast cancer patients were analyzed for SIPA1 and RRP1B polymorphisms with PCR-RFLP assay. SIPA1 c.2760G?>?A, c.545C?>?T and RRP1B c.436T?>?C polymorphisms were associated with lymph node status, survival and tumor grade, respectively. Our results suggest that SIPA1 and RRP1B germline polymorphisms are important for breast cancer prognosis.     

Vitamin D receptor ApaI,TaqI, BsmI,and FokI polymorphisms and psoriasis susceptibility: a meta-analysis

The aim of this study was to explore whether vitamin D receptor (VDR) polymorphisms confer susceptibility to psoriasis. Meta-analyses were conducted on the associations between the VDR ApaI, TaqI, BsmI, and FokI polymorphisms and psoriasis. Nine relevant studies on VDR polymorphisms and psoriasis were included in this meta-analysis, which involved 742 psoriasis patients and 715 controls. Meta-analysis indicated an association between the VDR ApaI A allele and psoriasis in Turkish studies (OR = 0.684, 95% CI = 0.475–0.985, p = 0.041). Meta-analysis indicated an association between the BsmI B allele and psoriasis in Asians (OR = 0.636, 95% CI = 0.411–0.984, p = 0.041), and showed a significant association between the FF and ff genotypes of the FokI polymorphism and psoriasis in all study subjects and in Turkish studies (OR = 2.028, 95% CI = 1.194–3.446, p = 0.009; OR = 3.582, 95% CI = 1.602–8.009, p = 0.002). This meta-analysis suggests that the VDR ApaI polymorphism confers susceptibility to psoriasis in the Turkish population. In addition, associations were found between the BsmI polymorphism and susceptibility to psoriasis in Asians and between the Fok I polymorphism and psoriasis in the Turkish population.     

Association of genetic variation in co-stimulatory molecule genes with outcome of liver transplant in Iranian patients

CD28, cytotoxic T-lymphocyte associated antigen 4 (CTLA4), inducible costimulator (ICOS) and programmed cell death 1 are closely-linked genes located on chromosome 2q and encode co-stimulatory molecules, which are T-cell activity regulators. The principal assignment of T-cell mediated immune response in allograft rejection is an interesting topic of multiple studies. Although the variation in these genes may influence the graft survival and the amount of immunosuppression needed, the studies so far have been restricted solely to the CTLA4 gene. In 145 patients who underwent liver allograft transplantation, 10 single nucleotide polymorphisms of CD28, CTLA4, ICOS, and PD.1 genes were defined. To distinguish the polymorphisms of all 10 SNPs, PCR-RFLP method was used and according to the standard criteria, acute rejection episodes were determined. CTLA4-1661, AA genotype was significantly more frequent in the patients with acute rejection and AG genotype was significantly more frequent in the patients without rejection. Frequencies of CTLA4+49 AG A allele and CTLA4-1661AG A allele were significantly higher than those of CTLA4+49 AG and CTLA4-1661AG, G allele in the patients with acute rejection. ICOS+693, GG genotype and G allele were significantly less frequent in the patients with acute rejection and CD28 CT genotype was significantly more in patients with acute rejection. The present results demonstrate that potentially functional genetic variation in T-cell co-stimulatory molecules including ICOS, CTLA4 and CD28 can influence liver transplant outcome.     

Analysis of CC chemokine receptor 5 and 2 polymorphisms and renal transplant survival

Chronic rejection is an immune process leading to graft failure. By regulating the trafficking of leukocytes, chemokines and chemokine receptors are thought to be one of the reasons causing acute renal rejection (ARE), which increases the possibility of chronic rejection and organ destruction. This study was designed to investigate, in the Turkish population, an association of chemokine receptor genetic variants, CCR2V641, CCR5-59029-A/G, CCR5-Delta32 and acute renal rejection after renal transplant surgery. We carried out our study in 85 Turkish renal transplant patients (45 men, 40 women; mean age 39 +/- 2 years) by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. We found no significant difference in the incidence of rejection among patients possessing or lacking CCR5-Delta32. For the groups with and without acute renal rejection, we found a significant difference between the groups in A and G allele distribution in both CCR2V641and CCR559029 gene variants (p = 0.003 and p = 0.003, respectively). According to our findings, the risk of acute rejection in renal transplantation may be associated with genetic variation in the chemokine receptor genes CCR5-59029 and CCR2V641 in Turkey, and studies on these gene polymorphisms could be an ideal target for future interventions intended to prevent renal transplant loss.