Influence of cytokine gene polymorphisms on graft rejection in Turkish patients with renal transplants from living related donors

Background

Certain cytokine gene polymorphisms (CGPs) have been shown to be associated with renal transplant rejection episodes or graft outcomes. We sought to evaluate the relationships between gene polymorphisms and acute rejection episodes (RG, n = 19) versus stable graft function (NRG, n = 71) in transplant recipients compared with healthy control subjects (HCG, n = 150). The follow-up time period was 18 months. Using polymerase chain reaction sequence-specific primers with the Heidelberg kit we genotyped 22 single nucleotide polymorphisms distributed across 13 cytokine and cytokine receptor genes.

Results

Interleukin (IL)-2 TT/GT haplotype was found in 36.8% of RG patients and 6.7% of HCG but not among the NRG (P < .0001; .0007). The IL-2 GG/TT haplotype was observed among 13 NRG and nine HCG patients (P = .007); the IL-2 GG/GG haplotype, 18.7% HCG and 4.2% NRG patients (P = .0033); and the IL-2 TT/TT haplotype, five NRG and eight HCG patients, but none of the RG cohort (P > .05). The transforming-growth factor-beta 1 CG/CC haplotype was noted in 15 NRG (21.1%) and four HCG but no RG patients (P < .0001). The IL-2 +166 GT genotype was detected in 36.8% of RG, 8.5% of NRG, and 14.7% of HCG patients (P = .005, .0244). The IL-2 −330 GG genotype was demonstrated in 32 healthy controls and three nonrejection transplant patients (P = .0007). Significant differences were concluded between NRG and HCG for IL-6 565 AG, IL-1beta −511 TT and +3962 CC/CT/TT genotypes.

Discussion

We observed significant differences among the frequencies of IL-2 gene polymorphisms among RG and NRG subjects, which agreed with previous clinical, but not in vitro studies.     

Human leukocyte antigen and major histocompatibility complex class I-related chain a antibodies after kidney transplantation in Turkish renal transplant recipients

Background

This study was designed to determine whether human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related A (MICA) antibody (Ab) production during the first 6 months posttransplantation correlated with long-term graft survival and rejection rate. The study group included 147 first transplantations from either living related (LRDs) or deceased donors (DDs) who were divided into two subgroups: rejection (RG, n = 28) and nonrejection (NRG, n = 119). Serum samples (n = 441) collected from each patient on posttransplant days 30, 90, and 180 were tested for HLA and MICA Ab using the Luminex technique.

Results

Among 82 Ab-positive patients (55.8%), 40 had both HLA and MICA, 33 only HLA, and 9 only MICA Ab in the posttransplant period. The rates of HLA class I, class II, or both Ab positivities were greater in the RG than the NRG (P = .011, .037, and .0275, respectively). At 180 days posttransplant, 64.3% of patients in the RG had Ab and 41.2% in the NRG (P = .0349). The data for the LRD (n = 116) group were similar to those for the entire group; whereas there was no significant difference in Ab positivity between RG and NRG patients who received organs from DDs. There was no significant difference with respect to HLA class II and/or MICA Ab positivity between RG and NRG among patients who lacked HLA class I Ab.

Discussion

We confirmed that HLA and MICA Ab may be harmful posttransplant, promoting rejection processes and representing an important cause of graft failure. HLA class II and MICA Ab positivities were only important predictors of graft failure when present together with HLA class I positivity. Patients who developed HLA alone or both HLA and MICA Ab rejected their grafts more frequently than Ab-negative recipients.     

Adiponectin gene polymorphisms are associated with posttransplantation diabetes mellitus in Chinese renal allograft recipients

Background

Posttransplantation diabetes mellitus (PTDM) is a well-recognized renal transplantation complication that is associated with increased graft loss, morbidity, and mortality. Adiponectin gene polymorphisms are associated with type 2 diabetes. However, it remains unknown whether these polymorphisms increase the risk for development of PTDM. Therefore, the aim of this study was to investigate the association between the adiponectin gene polymorphism and the risk of PTDM among Chinese renal allograft recipients.

Methods

We genotyped 398 unrelated renal allograft recipients without a prior diagnosis of diabetes, including 97 PTDM and 301 without PTDM, for adiponectin gene variants: single nucleotide polymorphisms at position 45 and 276, that is, SNP-45: T/G, SNP-276: G/T, using the polymerase chain reaction-restriction fragment length polymorphism assay. No prisoners or organs from prisoners were used in the study.

Results

The G allele of SNP-276 was significantly more frequent in PTDM than non-PTDM subjects (P = .041). For SNP-45 and SNP-276, the incidence of PTDM was significantly higher in patients with the GG genotype than those with the TG and TT genotypes (48.1% vs 21.5% and 23.6% and 30.7% vs 18.5% and 22.8%; (P = .011 and .024, respectively). Even after adjusting for age and sex, the effects of the SNP-45 genotypes for GG compared to TT (odds ratio [OR] = 3.108, P = .009) and GG compared to TG (OR = 3.620, P = .004) as well as for SNP-276 genotypes GG compared to TG (OR = 2.203, P = .002) and body mass index at transplantation (OR = 1.099, P = .024) remained significant.

Conclusions

These data suggested that SNP-45 and SNP-276 of the adiponectin gene were significantly associated with an increased risk for PTDM among Chinese renal allograft recipients.     

Influence of interleukin-6 promoter polymorphism -174 g/c on kidney graft outcome

Background

The cytokine interleukin-6 (IL-6) is important in both immune responses and cardiovascular diseases. The IL-6 promoter polymorphism −174 G/C is associated with increased plasma concentrations of IL-6. The relationship between IL-6 polymorphisms and graft survival, cardiovascular events, and new-onset diabetes mellitus after kidney transplantation is controversial.

Objective

To analyze whether IL-6 (−174 G/C) polymorphism influences kidney graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.

Methods

The IL-6 promoter polymorphism (−174 G/C) was analyzed using the polymerase chain reaction with sequence-specific primers in 335 kidney transplant recipients. Data for graft survival, chronic graft nephropathy, cardiovascular events, and new-onset diabetes were obtained retrospectively from clinical records. Categorical variables were compared between individuals with CC, GG, and GC genotypes using χ² tests. Survival analysis was performed using the Kaplan-Meier method, comparing groups using the log-rank test.

Results

No significant differences were observed in 5-year graft survival between individuals with CC and GC/GG genotypes (85.3% vs 77.1%; P = .22). Nor were significant differences noted in the rates of chronic allograft nephropathy (37.5% vs 33.8%; P = .48), cardiovascular events (10.0% vs 23.0%; P = .10), or new-onset diabetes (7.5% vs 11.8%; P = .28).

Conclusion

There is no association between IL-6 (−174 G/C) polymorphism and graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.     

Genetic polymorphisms of interleukin-1 beta and osteosarcoma risk

Purpose

Osteosarcoma is the most common childhood bone cancer. Interleukin-1 beta (IL-1B) is crucially involved in osteosarcoma carcinogenesis. Whether genetic polymorphisms of IL-1B also influence osteosarcoma risk is unknown. The aim of this study was to investigate the association between IL-1B gene polymorphisms and osteosarcoma risk in Chinese Han patients.

Methods

A hospital-based case–control study involving 120 osteosarcoma patients and 120 controls was conducted. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect three IL-1B gene polymorphisms (−31 T/C, −511 C/T and +3954 C/T) in these patients.

Results

Patients with osteosarcoma had a significantly lower frequency of −31 CC genotype [odds ratio (OR) = 0.40, 95 % confidence interval (CI) = 0.17–0.92; P = 0.03] and −31 C allele (OR = 0.67, 95 % CI = 0.46–0.99; P = 0.04) than controls. Patients with osteosarcoma had a significantly lower frequency of −511 TT genotype (OR = 0.40, 95 % CI = 0.17–0.95; P = 0.04) than controls. The +3954 C/T gene polymorphisms were not associated with a risk of osteosarcoma. When stratified by Enneking stage, tumour location, histological type, tumour metastasis of osteosarcoma and family history of cancer, no statistically significant results were found.

Conclusions

This is the first study to provide evidence for an association of IL-1B gene polymorphisms with osteosarcoma risk.     

The estrogen receptor α gene (XbaI,PvuII) polymorphisms and susceptibility to idiopathic scoliosis: a meta-analysis

Study design

A genetic association meta-analysis of estrogen receptor α gene (ERα) polymorphisms with idiopathic scoliosis.

Objective

To determine whether the ERα gene polymorphisms correlate with idiopathic scoliosis.

Summary of background data

Idiopathic scoliosis represents a complex genetic trait under the influence of multiple predisposition genes. Several studies showed that single nucleotide polymorphism (SNP) in ERα was associated with idiopathic scoliosis, but the results from some studies were conflicting.

Methods

We searched PubMed, EMBASE, and Cochrane CENTRAL databases from January 1994 to January 2014. All the case–control studies included should mainly study the relationship between XbaI A/G, PvuII T/C polymorphisms and the susceptibility of idiopathic scoliosis.

Results

A total of 299 articles were found, six of which fulfilled the inclusion criteria after being assessed by two reviewers. A pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to assess the associations. Subgroup meta-analyses were performed according to ethnicity. Overall, ERα Xbal A/G polymorphism was not associated with risk of idiopathic scoliosis (G versus A, OR 1.07, 95 % CI 0.88–1.30, P = 0.51; AG versus AA, OR 1.03, 95 % CI 0.89–1.21, P = 0.67; GG versus AA, OR 1.12, 95 % CI 0.72–1.73, P = 0.61; AG/GG versus AA, OR 1.05, 95 % CI 0.91–1.22, P = 0.49; GG versus AG/AA, OR 1.10, 95 % CI 0.75–1.63, P = 0.62). ERα PvuII T/C polymorphism was also not associated with risk of idiopathic scoliosis under five models (C versus T, OR 0.93, 95 % CI 0.75–1.14, P = 0.48; TC versus TT, OR 0.99, 95 % CI 0.80–1.23, P = 0.93; CC versus TT, OR 1.05, 95 % CI 0.80–1.39, P = 0.72; TC/CC versus TT, OR 1.01, 95 % CI 0.83–1.23, P = 0.93; CC versus TC/TT, OR 1.05, 95 % CI 0.82–1.33, P = 0.72).

Conclusion

ERα Xbal and ERα PvuII polymorphisms are not obviously associated with risk of idiopathic scoliosis.     

Cytokine Gene Polymorphisms in Kidney Transplantation

Background

Acute and chronic rejections remain an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may have a predictive role to identify patients at greater risk of rejection regardless of human leukocyte antigen (HLA) compatibility and/or the presence of anti-HLA antibodies before the renal allograft.

Objectives

We sought to investigate polymorphisms of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, interleukin (IL)-10, IL-6, and interferon (IFN)-γ as indices of differential cytokine production in kidney transplantation and to examine their predictive roles for acute or chronic rejection.

Patients and Methods

TNF-α (G/A -308), TGF -β1 (haplotype codon 10/codon 25), IL-10 (haplotype-1082, −819, −592), IL-6 (C/G -174), and IFN-γ (T/A +874) single nucleotide polymorphisms (SNPs) were detected using polymerase chain reaction (PCR)-specific sequence primers (SSP) in 231 kidney transplant recipients (KTR) including 106 treated with mycophenolate mofetil (MMF+).

Results

We observed no significant associations of any of investigated polymorphism taken alone with acute rejection episodes (ARE) or chronic allograft dysfunction (CAD). Nevertheless, TGF-β1 Low (L) production was correlated with greater graft survival at 20 years (81.8%) compared with intermediate (L) or high (H) levels (56.1%), affect that the difference was not significant (P = .2). Cytokine haplotype analysis in KTR (MMF−) without HLA-mismatches or presynthesized anti-HLA antibodies (n = 32) showed ARE to be significantly more prevalent among the TNF-α*H/TGF- β1*H/IL-10*H production haplotype (75%) compared with the other haplotypes (16%; P = .03).

Conclusion

The presence of TGF-β1-H secretion profile may protect the kidney graft. TNF-α*H/TGF-β1*H/IL-10*H haplotype was associated with a higher risk of ARE and with poorer graft survival.     

Primary Cutaneous Melanoma with Regression Does not Require a Lower Threshold for Sentinel Lymph Node Biopsy

Introduction Histological evidence of primary tumor regression (RG) is observed in 35% or fewer patients with cutaneous melanoma. Some advocate a lower threshold for sentinel lymph node (SLN) biopsy when RG is present. Methods We identified 1,349 patients presenting to our center with clinically localized cutaneous melanoma between 1995 and 2004. Of these, 344 demonstrated histological RG in their primary melanoma. A retrospective analysis of their medical records was performed to obtain clinical and pathological information. Results The median Breslow depth for the 344 patients with RG was 1.1 mm versus 1.5 mm for 1,005 patients with no regression (NRG) (P < 0.005). SLN biopsy was performed in 64% of patients with RG and 72% without. Positive SLN was more common in those with NRG than in those with RG (18% vs 10%, P = 0.005). Only one RG patient with thin melanoma (≤1 mm, Clark IV) had a positive SLN. When stratified by Breslow depth, patients with RG had lower rates of SLN positivity in all groups (≤1.0mm, >1.0 and ≤2.0mm, >2 and ≤4 mm, and >4.0 mm). Recurrence was more common in patients with NRG (21% vs 12%; P < 0.005). Both local and systemic recurrence occurred more commonly in patients with NRG (4% vs 1%, P = 0.002 and 8% vs 3%, P < 0.005, respectively) Conclusions The presence of histological RG in a primary melanoma predicts neither SLN positivity when stratified by Breslow depth nor increased risk of recurrence when compared with melanomas with NRG.     

The Association of Caveolin-1 Genotypes with Oral Cancer Susceptibility in Taiwan

Background

Caveolin-1, which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. The aim of this study was to evaluate the association between oral cancer susceptibility and Cav-1 genotypes. In this hospital-based case-control study, the association of Cav-1 polymorphisms with oral cancer risk in a central Taiwanese population was investigated.

Methods

Six hundred patients with oral cancer and 620 age- and sex-matched healthy control subjects were genotyped and analyzed by polymerase chain reaction–restriction fragment length polymorphism.

Results

There were significant differences between oral cancer and control groups in the distributions of their genotypes (P = 1.7 × 10^?18 and 2.6 × 10^?4) and allelic frequencies (P = 3.3 × 10^?19 and 9.5 × 10^?6) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) polymorphisms, respectively. As for the combined genotype analysis, those who had GG/AT or GG/AA at Cav-1 G14713A/T29107A showed a 0.72-fold (95% confidence interval = 0.52–0.99) decreased risk of oral cancer compared to those with GG/TT, while those of any other combinations were of increased risk. The presence of metastasis was also correlated to both Cav-1 G14713A AA and Cav-1 T29107A TT genotypes.

Conclusions

Cav-1 is involved in oral cancer, the A allele of the Cav-1 G14713A is risky, the A allele of the Cav-1 T29107A is protective, and AA/TT on these two polymorphisms may be the most risky combined genotype for the development of oral cancer and may be novel risk markers for early detection and prediction of distant metastasis.     

Possible association of Toll-like receptor 9 polymorphisms with cytokine levels and posttraumatic symptoms in individuals with various types of orthopaedic trauma: Early findings

Background

Although TLR9 polymorphisms may be associated with cytokine dysregulation, its role in regulation of cytokines due to bodily trauma or in relation to acute stress symptoms or posttraumatic stress symptoms (ASS/PTS) has not been evaluated.

Aims

To assess serum cytokine levels and levels of ASS and PTS in relation to four common TLR9 single-nucleotide polymorphisms (SNPs) in individuals with various types of orthopaedic trauma.

Methods

Forty-eight accident-injured individuals, aged 20–60 years were studied. Serum cytokine levels and TLR9 SNPS (1486T/C, 1237T/C, 1174G/A and 2848G/A) were assessed together with intensity of ASS and PTS symptoms.

Results

Statistically significant higher serum levels of IL-12 and IL-1β (p < .05) were found in individuals heterozygous for TLR9-1237 (TC) than in individuals expressing the most common TLR9-1237 type (TT), while differences in levels of IL-6 were not significant. Also, marginally significant levels of IL-6 were found in individuals expressing the common TLR9-1174 (GG) compared with individuals homozygous (AA) or heterozygous (GA) for this SNP. They also had non-significant higher intensity of ASS symptoms. A trend of higher PTS levels in individuals expressing the most common type TLR9-1174 (GG) was found, contrary to homozygous (AA) and heterozygous individuals (GA).

Conclusions

The results of this pilot study suggest that accident-injured individuals with certain TLR9 polymorphisms express higher levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-12). The associations of TLR9 SNPSs with increased risk of ASS or PTS should be further studied in larger groups of such patients.     

CTLA-4 exon 1 +49A/G polymorphism is associated with renal involvement in pediatric Henoch–Sch?nlein purpura

Background

Henoch–Sch?nlein purpura (HSP) is a multisystemic vasculitis of unknown etiology. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and CD28 have been reported to be important candidate genes for conferring susceptibility to autoimmunity. In this study, we investigated the correlation of CTLA-4 and CD28 gene polymorphisms with HSP in children with and without renal involvement.

Methods

The CTLA-4 exon 1 +49A/G, promoter -318C/T and CD28 IVS3 +17T/C single nucleotide polymorphisms (SNPs) were genotyped in 110 children with HSP and 90 ethnically matched healthy controls through restriction fragment-length polymorphism (RFLP).

Results

The CTLA-4 (+49) GG genotype and G allele (GG + AG genotype) were more common in HSP patients with renal involvement (n?=?52) than in HSP patients without renal involvement (n?=?58) (P?=?0.019 and 0.001, respectively). There were no significant differences in the prevalence of CTLA-4 (+49 A/G), (-318C/T) and CD28 IVS3 (+17 /T/C) polymorphisms between HSP patients and controls.

Conclusions

Our findings suggest that the CTLA-4 +49 GG genotype and G allele may contribute to increased risk for the development of renal damage in HSP patients.     

Association of 276G>T adiponectin gene polymorphism to plasma adiponectin and albuminuria in type 2 diabetic patients

Purpose

The 276G>T polymorphism of the adiponectin (ADIPOQ) gene has been correlated with plasma adiponectin, type 2 diabetes (T2D) and its complications. Studies of the role of 276G>T polymorphism in the prevalence of T2D kidney disease are few and contradictory; ethnic differences might play a role. We aimed to assess the relationship of this polymorphism with albuminuria in a cohort of Caucasian T2D patients.

Methods

Consecutive T2D outclinic patients were screened and included upon informed consent; exclusion criteria were glomerular filtration rate (GFR) <30?ml/min, acute intercurrent illness and urinary tract infection. History, standard laboratory evaluation, total plasma adiponectin and genotyping for the 276 ADIPOQ locus were obtained.

Results

One hundred and three T2D patients were included. Forty-three (41.7%) of them had GG genotype, 50 (48.5%) had GT and 10 (9.7%) had TT genotype. Plasma adiponectin was significantly higher in TT-allele carriers (19.03?±?3.46???g/ml) than in GT (10.14?±?1.78???g/ml) and GG carriers (8.71?±?1.60???g/ml), P?=?0.003. Adiponectin was higher in albuminuric (13.97?±?2.07???g/ml) than in normoalbuminuric patients (6.91?±?0.88???g/ml), P?=?0.004. The prevalence of T allele was higher in normoalbuminuric patients [36 (69.2%) GT?+?TT carriers] than in albuminuric ones [24 (47.1%)], P?=?0.02. Logistic regression identified the following as predictors of albuminuria: GG genotype: P?=?0.003 (OR 4.2; CI 1.61?C10.96); low GFR: P?=?0.003 (OR 0.97; CI 0.95?C0.99); and high plasma adiponectin: P?=?0.012 (OR 1.07; CI 1.01?C1.14).

Conclusions

Our data suggest that 276G>T polymorphism of the ADIPOQ gene is associated with plasma adiponectin levels. By influencing adiponectinemia, 276G>T polymorphism might predict the presence of albuminuria in Caucasian T2D patients.     

Angiotensinogen t235 and angiotensin-converting enzyme insertion/deletion polymorphisms associated with the development of posttransplantation diabetes mellitus in renal allograft recipients

Background

Genetic polymorphisms of the renin-angiotensin system (RAS) have been reported to play an important role in the pathogenesis of diabetes mellitus and hypertension. In addition, a close association has been reported between RAS and the progression of both diabetes and hypertension. But the role of RAS on the development of posttransplantation diabetes mellitus (PTDM) is not known. For this purpose we investigated the association of polymorphisms in the genes for angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) with the development of PTDM.

Methods

Genotyping for ACE insertion/deletion (I/D) and AGT M235T polymorphisms was performed in 50 patients who underwent renal transplantation during a 5-year period. Group 1 consisted of 23 recipients who developed PTDM and group 2 consisted of 27 recipients that did not have PTDM.

Results

Of 50 patients, 13 (26%) showed the ACE DD, 21 (42%) the ACE ID, and 16 the ACE II genotype. The frequencies of AGT MM, AGT MT, and AGT TT were 0, 54%, and 46%, respectively. Compared with group 2, there were high frequencies of the AGT TT genotype in group 1 recipients (P < .001). In addition the ACE DD genotype was found significantly higher in group 1 patients compared with group 2 patients (P = .001).

Conclusion

The high frequencies of the AGT TT genotype and ACE DD genotype in recipients may contribute to the high prevalence of PTDM. Our data suggest a synergistic effect between the ACE and AGT polymorphism in the risk of PTDM, but to support this theory a larger patient group must be studied.     

Total thyroidectomy for benign disease in the pediatric patient—feasible and safe

Purpose

Total thyroidectomy (TT) is a safe and efficacious treatment of malignant thyroid disease in children. The role of TT in benign thyroid disease is less well-defined. The goal of this study was to compare the safety of TT performed for benign and malignant disease.

Methods

The medical records of 31 patients undergoing TT from January 2000 to June 2007 at a single center were reviewed. The benign cohort totaled 15 patients consisting of 12 with Graves' disease, 2 with hyperthyroidism, and 1 with large and symptomatic multinodular goiter. The malignant cohort totaled 16 patients consisting of 9 with malignant disease, 4 with a nodule and history of cancer or radiation exposure, and 3 with RET proto-oncogene mutations.

Results

The most common complication was transient hypocalcemia observed in 7 (46%) of 15 patients with benign disease and 9 (56%) of 16 patients with malignancy (P = .72). Permanent hypocalcemia, defined as need for calcium supplement 6 months postprocedure, was observed in 1 patient with benign disease (6.67%) and 1 patient with malignancy (6.25%; P = 1.0). A single parathyroid gland was reimplanted in 2 patients with malignancy and 2 patients with benign disease (P = 1.0). One case of keloid scar was noted, and no cases of recurrent laryngeal nerve palsy, nerve paralysis, tracheal injury, tracheostomy, or wound infection were encountered in either cohort. There were no cases of relapse hyperthyroidism in the benign cohort.

Conclusions

Similar rates of postoperative complications can be expected with TT for benign thyroid disease as compared to TT for malignant disease. Total thyroidectomy is a safe treatment option for benign thyroid disease in children.     

Hypoxia and renal cell carcinoma: The influence of HIF1A+1772C/T functional genetic polymorphism on prognosis

Objectives

Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular response to hypoxia. Overexpression of HIF-1 has been implicated in the pathogenesis of renal cell carcinoma (RCC), and functional polymorphisms of the HIF1A gene may confer susceptibility to RCC. Our purpose was to assess the influence of HIF1A+1772C/T (rs11549465) polymorphism on RCC prognosis.

Genetic Association of Tumor Necrosis Factor-β, Interleukin-10, and Interleukin-1 Gene Cluster Polymorphism With Susceptibility to Pneumonia in Kidney Transplant Recipients

Introduction

Pneumonia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was therefore conducted to investigate whether or not the polymorphisms of tumor necrosis factor (TNF)β, interleukin (IL)-10, IL-1β, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation.

Methods

Subjects comprised 33 kidney transplant recipients with pneumonia and 63 noninfected kidney transplant recipients. Genomic DNA from these 96 kidney transplant recipients was extracted from peripheral blood leukocytes. The regions containing the NcoI polymorphic site at position +252 of TNFβ gene, the RsaI polymorphic site at position −592 of IL-10 gene, and the AvaI polymorphic site at position −511 of IL-1β gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI, RsaI, and AvaI restriction enzyme, respectively. The polymorphic regions with intron 2 of the IL-1 ra gene (IL-1 RN) containing variable numbers of a tandem repeat of 86 base pairs, were amplified by PCR.

Results

Univariate analysis showed that recipient IL-10, IL-1β, and IL-1 RN polymorphisms were not associated with the presence of pneumonia (P = .589, .940, and .286, respectively). However, compared with GG genotype, recipient TNFβ +252AA + AG genotype was significantly associated with susceptibility to pneumonia (P = .006). Age of 45 years or older was not significantly associated with susceptibility to develop pneumonia but had a tendency to develop it (P = .119). After adjusting for age of 45 years or older, recipient TNFβ+252 AA + AG genotype (odds ratio = 5.366, 95% confidence intervals = 1.470 − 19.589, P = .011) independently predicted the risk for pneumonia within the first year after kidney transplantation in the multivariate analysis.

Conclusion

These results suggested that recipient TNFβ gene polymorphism may be useful in predicting pneumonia, hence identifying individuals who could benefit from preventive treatment and a less potent immunosuppression regimen.     

Interleukin-17 and Kidney Allograft Outcome

Acute rejection episodes (ARE) are important complications that involve the interplay between mechanisms that maintain graft tolerance and promote rejection. The proinflammatory cytokine interleukin-17 (IL-17) has been implicated in many conditions in humans and mice. In kidney transplant patients, the evaluation IL-17 levels has been performed in only a few patients. We performed a cross-sectional study correlating quantitative IL-17 levels and clinical outcomes.

Patients and methods

We studied 19 specimens from biopsies performed in patients (n = 19) who received isolated kidney grafts. ARE signs were present in 9 (47%) patients who provide specimens; whereas, 10 (53%) others showed no signs of rejection. Eighteen healthy control sample IL-17 underwent measurement, all of which were performed by an enzyme-linked immunosorbent assay method. We assessed other factors, such as the recipients demographic data, cold ischemia time, HLA mismatches, time elapsed from transplantation to the biopsy, posttransplantation status, antibody panel, donor type, and immunosuppressive treatment.

Results

IL-17 levels were clearly increased among samples derived from patients with ongoing rejection (125.7 ± 27.06 pg/mL) in contrast, to the nonrejection group, (30 ± 13.32 pg/mL) (P < .05). Healthy controls showed no detectable IL-17 levels.

Conclusions

These findings suggested that IL-17 was important in the pathophysiology of acute kidney rejection.     

Gene polymorphisms contributing to hypertension in immunoglobulin A nephropathy

Background

Hypertension, which is affected by genetic and environmental factors, is one of the major risk factors for chronic kidney disease. Identification of the genetic factor contributing to hypertension in patients with chronic kidney disease may potentially refine a therapeutic strategy.

Methods

In the present multicenter cross-sectional study, 240 patients were eligible (aged 15?C50?years with urinary protein ??0.25?g/day) out of 429 patients who were diagnosed as having immunoglobulin (Ig) A nephropathy (IgAN) by renal biopsy between 1990 and 2005 and enrolled in our previous study, PREDICT-IgAN. The outcome was hypertension defined as ??140 and/or ??90?mmHg of systolic and diastolic blood pressure and/or use of antihypertensives at renal biopsy. We assessed associations between hypertension and 28 polymorphisms with the frequency of minor genotype ??10% among 100 atherosclerosis-related polymorphisms using the Chi-squared test in dominant and recessive models. We identified polymorphisms associated with hypertension in multivariate logistic regression models.

Results

Baseline characteristics: hypertension 36.3%. Among 28 polymorphisms, the Chi-squared test revealed that CD14 (-159CC vs CT/TT, P?=?0.03) and ACE (DD vs DI/II, P?=?0.03) were significantly associated with hypertension after Bonferroni correction. Multivariate logistic regression models revealed that CD14 -159CC [vs CT/TT, odds ratio (OR) 3.58 (95% confidence interval (CI) 1.66?C7.63)] and ACE DD [vs DI/II, OR 4.41 (95% CI 1.80?C10.8), P?=?0.001] were independently associated with hypertension.

Conclusions

CD14 C-159T and ACE I/D contributed to hypertension in patients with IgAN.     

Impact of Gastrografin in clinical practice in the management of adhesive small bowel obstruction

Background

Gastrografin (GG) has been shown to accelerate the resolution of adhesive small bowel obstruction (ASBO) and decrease length of stay (LOS) in hospital. Consequently, we instituted a protocol recommending the routine use of GG in patients with ASBO. This study reviews patient outcomes after protocol implementation.

Methods

We conducted a retrospective review of all patients with ASBO from January 1997 to December 2007. Data were categorized by admission date and use of GG. The outcomes reviewed were protocol uptake, median LOS in hospital and operative rate. Results were analyzed using the Mann–Whitney U test and the 2-tailed Fisher exact test.

Results

There were 710 patients with ASBO overall. Sixteen of 376 (4.3%) patients received GG before institution of the protocol (period 1), whereas 195 of 334 (58.4%) received GG thereafter (period 2). In period 2, use of GG was limited to between 58% and 69% of all potentially eligible patients per year. Fifty-seven of 710 (8%) patients required surgery. In period 1, there were no significant differences in median LOS in hospital (p = 0.29) and operative rate (p = 0.65) between patients who received GG and those who were managed without GG. In period 2, patients receiving GG had a greater median LOS in hospital (3 [range 2–5] v. 2 [range 1–5] d, p = 0.048) but significantly lower operative rates (5.1% v. 12.9%, p = 0.018). Overall, the median LOS decreased over time (period 1: 4 [2–7] d v. period 2: 2 [1–5] d, p = 0.010). The operative rate did not vary substantially bewteen periods (7.7% v. 8.4%, p = 0.42).

Conclusion

The introduction of a protocol has increased the proportion of eligible patients receiving GG. However, protocol nonadherence and factors other than GG usage have influenced LOS in hospital and operative rates. Demonstrated benefits from previously published clinical trials have thus not been replicated within our setting.     

Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus

Purpose

Nitric oxide (NO), a short-lived gaseous free radical, is a potent mediator of biological responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Nitric oxide also serves as an important signal in physiological processes, including angiogenesis, thrombosis, and bone turnover, which are known to be related to the pathogenesis of osteonecrosis. We investigated whether NOS3 gene polymorphisms are associated with risk of osteonecrosis of the femoral head (ONFH).

Methods

Five polymorphisms in the NOS3 gene were genotyped using TaqMan assays in 306 controls, 150 SLE patients, and 50 SLE patients with ONFH (SLE_ONFH).

Results

We found that Asp258Asp and Glu298Asp (G894T) polymorphisms in the NOS3 gene were significantly associated with risk of ONFH. Additionally, we calculated haplotype frequencies of a linkage disequilibrium (LD) block in NOS3 (rs1799983???rs1800780) and tested for haplotype associations. The haplotypes G-A and T-A showed significant protective (P?=?1.6?×?10^-3; OR 0.39, 95 % confidence intervals (CI) 0.22–0.7) and increased risk (P?=?2.0 x 10^-5–6.0 x 10^-4; OR 3.17?3.73) effects for ONFH, respectively.

Conclusions

These results suggest that exonic NOS3 polymorphisms may increase the risk of ONFH in Korean SLE patients