Study of programmed cell death 1 (PDCD1) gene polymorphims in Iranian patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by axial arthritis in which the genetic-environmental factors seem to be involved in the pathogenesis of the disease. This study was performed to investigate the role of polymorphisms of the programmed cell death 1 (PDCD1) gene on susceptibility to AS. In this study, 161 Iranian patients with AS and 208 normal controls were enrolled; two single-nucleotide polymorphisms (SNPs) of the PDCD1 gene PD-1.3 (G, A) in nucleotide position +7146 of intron 4 and PD-1.9 (C, T) in nucleotide +7625 of exon 5 were studied. Analysis of PD-1.3 revealed that 82% of patients and 79% of controls had GG genotype, while GA and AA genotypes were detected in 17% and 0.6% of patients, respectively, and 20% and 1.4% of controls, respectively. Moreover, the genotype CC (PD-1.9) was present in 92% of patients and 97% of controls. Although these differences were not statistically significant between patients and controls, comparisons of genotypes frequencies in the AS patients, based on human leukocyte antigen (HLA)-B27, revealed that all patients who had CT genotype (PD-1.9) were HLA-B27 positive, whereas 30% of patients with CC genotype were HLA-B27 negative. There was no evidence of association for PDCD1 SNPs with AS in our study, but CT genotype (PD-1.9) seems to be associated with HLA-B27 positivity in the patients with AS.     

Serum Fetuin-A and Pentraxin3 in hemodialysis and renal transplant patients

ObjectiveThe aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients.MethodSerum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods.ResultsIn the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09–20.36) ng/mL vs. 1.65(0.24–7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75–81.48) ng/mL vs. 38.76(22.26–89.07) ng/mL, p = 0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1–8.50) mg/L vs. 1.1(0.1–7.9) mg/L, p = 0.003].ConclusionAlthough our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.     

Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome

Introduction

Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control.

Methods

This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-α), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects.

Results

Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P?=?0.017), IL-6 G allele at position ?174 (P?=?0.002), and TNF-α G allele at position ?238 (P?<?0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (?174) and TNF-α GG genotype (?238) in the patient group were also significantly overrepresented (P?<?0.001), while IL-6 CG genotype (?174) and TNF-α GA genotype (?238) were significantly decreased in the patients with IBS (P?<?0.001). The frequencies of IL-6 (?174, nt565) GG haplotype and TNF-α (?308, ?238) GG haplotype were also significantly higher in the patient group (P?<?0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-α GA were significantly decreased in the patients with IBS (P?<?0.001).

Conclusion

IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.     

In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated.     

T-Helper 1, T-Helper 2, and T-Regulatory Cytokines Gene Polymorphisms in Irritable Bowel Syndrome

Inflammation and mucosal immune system activation have an important role in irritable bowel syndrome (IBS), whereas genetic factors can control some immunological mediators. In this study, a number of polymorphic genes coding for T-helper 1, T-helper 2, and T-regulatory cytokines were genotyped in 71 patients with IBS, and the results were compared with controls. IL-4 CC genotype at position −590, IL-4 TT genotype at position −33, and IL-10 GA genotype at position −1082 were significantly overrepresented in the patients with IBS in comparison with controls (P < 0.001). The frequencies of the following haplotypes in the patient group were significantly higher than in the control group: IL-2 (−330, +160) GT haplotype (P = 0.002), IL-4 (−1098, −590, −33) TCC haplotype (P < 0.001), and TCT haplotype (P < 0.001). While production of cytokines could be affected by genetic polymorphisms within coding and promoter regions of cytokine genes, IL-4 and IL-10 gene polymorphisms could affect individual susceptibility to IBS.