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Öğe BLK pathway-associated rs13277113 GA genotype is more frequent in SLE patients and associated with low gene expression and increased flares(Springer London Ltd, 2017) Pamuk, Omer Nuri; Gurkan, Hakan; Pamuk, Gulsum Emel; Tozkir, Hilmi; Duymaz, Julide; Yazar, MetinWe aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes (p values < 0.01). The relative expression of Blk gene was significantly decreased in the SLE group as compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions of Blk and ZAP70 were significantly lower in SLE patients who had flares according to the SELENA-SLEDAI flare index when compared to those in others (p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients.Öğe BLK Pathway-Associated rs13277113 GA Genotype Is More Frequent in Systemic Lupus Erythematosus Patients and Associated with Low Gene Expression and Increased Flares(Wiley, 2015) Pamuk, Omer Nuri; Gurkan, Hakan; Balci, Mehmet Ali; Tozkir, Hilmi; Duymaz, Julide; Sari, Gulce; Yazar, Metin[Abstract Not Available]Öğe CASP10, LEF1, BCL2 genes are hypomethylated and CDKN2B is hypermethylated in chronic lymphocytic leukemia(Taylor & Francis Ltd, 2015) Pamuk, Gulsum Emel; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Tozkir, Hilmi; Pamuk, Omer Nuri[Abstract Not Available]Öğe CXCL12 rs18011157 polymorphism in patients with non-Hodgkin's lymphoma: Is it associated with poor outcome?(Wolters Kluwer Medknow Publications, 2018) Pamuk, Gulsum Emel; Tozkir, Hilmi; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Pamuk, Omer NuriObjective: We studied CXCL12-related rs18011157 polymorphism in non-Hodgkin lymphoma (NHL) patients. We also determined the effect of this polymorphism on clinical features and outcome of NHL. Methods: We included 90 NHL patients (54 males, 36 females) and 88 healthy controls (54 males, 34 females). CXCL12-related rs18011157 polymorphism was determined by polymerase chain reaction. Results: rs18011157 polymorphism was significantly more frequent in NHL patients with GA genotype than in healthy controls (37.8% vs. 20.5%, P = 0.011). The frequency of patients with initially high lactate dehydrogenase (LDH) level (65.8% vs. 38.5%) and extranodal involvement (61.1% vs. 43.8%) was significantly higher in the GA plus AA genotype groups when considered altogether (P = 0.01 and 0.09). Poor prognostic factors in univariate analysis were the presence of B symptoms, initially high International Prognostic Index (IPI), splenomegaly, nonresponse to first-line therapy, the presence of early relapse, and carrying A allele (GA plus AA genotypes). The independent prognostic factors in multivariate analysis were only early relapse and an initially high IPI score. Discussion: CXCL12 rs1801157 polymorphism which was found to be associated with extranodal involvement and increased LDH in NHL might be a marker of poor prognosis in patients with GA and AA genotypes. Conclusions: CXCL12-related rs18011517 polymorphism was more frequent in NHL patients: it might be associated with NHL pathogenesis and outcome.Öğe Increased frequency of class I and II anti-human leukocyte antigen antibodies in systemic lupus erythematosus and scleroderma and associated factors: a comparative study(Wiley, 2016) Tozkir, Hilmi; Pamuk, Omer Nuri; Duymaz, Julide; Gurkan, Hakan; Yazar, Metin; Sari, Gulce; Tanrikulu, HazelAim: There is significant autoantibody production in systemic lupus erythematosus (SLE) and scleroderma (SSc); microchimerism is also thought to play a role in pathogenesis. We determined the frequency of anti-HLA antibodies in SLE and SSc patients and evaluated associated clinical factors. Methods: We included 77 SLE patients, 46 SSc patients and 53 healthy controls into the study. Clinical data about the patients were obtained from hospital records. Anti-human leukocyte (anti-HLA) antigen antibody analysis of sera was performed by applying Lifecodes anti-HLA Class I and Class II Screening kits based on xMAP technology. Results: The frequencies of class I and II anti-HLA antibodies were significantly higher in SLE (27.3% and 41.6%) and SSc (26.1% and 41.3%) groups than in healthy controls (1.9% and 5.7%) (all P < 0.001). Frequencies of thrombocytopenia (P = 0.021), anti-ribonucleoprotein (P = 0.037) and anti-Ro (P = 0.027) were significantly higher in the class I antibody-positive SLE group; however, pericarditis was less frequent (P = 0.05). On the other hand, the class II antibody-positive SLE group had more frequent anti-ribosomal P antibody (P = 0.038), but less frequent active disease (P = 0.038). In the SSc group, class I antibody-positive patients had more frequent digital ulcers (P = 0.048) and anti-centromere antibodies (P = 0.01). There was no association of anti-HLA antibodies with pulmonary hypertension and interstitial fibrosis in SSc patients. Conclusions: Both class I and class II antibodies were found to be significantly increased in SLE and SSc. Rather than major organ involvement, anti-HLA antibodies were associated with the presence of other antibodies in both diseases.Öğe Natural killer cell killer immunoglobulin-like gene receptor polymorphisms in non-Hodgkin lymphoma: possible association with clinical course(Taylor & Francis Ltd, 2015) Pamuk, Gulsum Emel; Tozkir, Hilmi; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Pamuk, Omer NuriNatural killer (NK) cell killer immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of many diseases. We determined the association between polymorphisms of KIR and their ligands and susceptibility to non-Hodgkin lymphoma (NHL), clinical features and prognosis. We included 90 patients with NHL and 94 controls. In the NHL group, KIR2DS1, HLA-Bw4 (Thr80) and HLA-Bw4 (Thr80)+/Bw4 (Iso80)- ligands were significantly more frequent. Patients with early-stage NHL had more frequent KIR2DL5 and KIR2DL5B than patients with advanced-stage NHL. During a median follow-up of 27 months, 26 patients with NHL died. Poor prognostic factors in univariate analysis were KIR2DL5A, KIR2DS1 and KIR3DS1 genotypes. In multivariate Cox regression analysis, advanced age and early relapse were poor prognostic factors. KIR genes and ligands had no significant effect on survival. The activating KIR2DS1 gene might activate NK cells, contributing to the production of more lymphoma cells. In addition, KIR2DS1, KIR2DL5A and KIR3DS1 might also be associated with a poor prognosis in NHL.Öğe PECAM-1 GENE Polymorphisms and Soluble PECAM-1 LEVEL in Rheumatoid Arthritis and Systemic LUPUS Erythematosus Patients Is There a Link with Clinical Atherosclerotic Events?(Wiley, 2014) Pamuk, Omer Nuri; Tozkir, Hilmi; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Donmez, Salim; Yazar, Metin[Abstract Not Available]Öğe PECAM-1 gene polymorphisms and soluble PECAM-1 level in rheumatoid arthritis and systemic lupus erythematosus patients: any link with clinical atherosclerotic events?(Springer London Ltd, 2014) Pamuk, Omer Nuri; Tozkir, Hilmi; Uyanik, Mehmet Sevki; Gurkan, Hakan; Saritas, Fatih; Duymaz, Julide; Donmez, SalimGenetic polymorphisms of platelet endothelial cell adhesion molecule-1 (PECAM-1) were found to play roles in atherosclerotic events. We determined PECAM-1 polymorphisms, soluble PECAM-1, and CD40L levels in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and evaluated their associations with clinical atherosclerotic complications. We included 100 RA patients, 81 SLE patients, and 94 healthy controls. The clinical features about the patients were obtained from medical records. Past cardiovascular complications were recorded. The most frequent gene polymorphisms of PECAM-1 were studied in our genetics laboratory. Soluble PECAM-1 and CD40L levels in serum were determined with ELISA. The frequencies of 373C (rs668) and 1688A (rs12953) alleles were higher in RA patients when compared to controls (p values, 0.028 and 0.016). RA and SLE patients had significantly higher allele frequencies for 2008A (rs1131012) when compared to controls (p values, 0.016 and 0.001). SLE patients had significantly more frequent AA genotype for rs1131012 polymorphism than RA patients and controls (p values, 0.007 and < 0.001). Soluble PECAM-1 level was significantly higher in RA patients than in SLE patients and healthy controls (p values < 0.001). Atherosclerotic complications were more frequent in SLE patients with AG genotype (rs12953) than those with AA genotype (p = 0.021). SLE patients with CC genotype (rs668) had a significantly lower frequency of atherosclerotic complications than those with CG genotype (p = 0.045). Nevertheless, in multivariate analysis, there was no association between genotype and atherosclerotic complications. We found associations between various PECAM-1 polymorphisms in RA and SLE; PECAM-1 and soluble CD40 ligand (sCD40L) levels were significantly higher in RA patients than in SLE and control groups. PECAM-1 polymorphisms in SLE were protective against atherosclerotic complications.Öğe The significance of KIR gene polymorphisms in chronic lymphocytic leukemia(Taylor & Francis Ltd, 2015) Pamuk, Gulsum Emel; Akpinar, Seval; Tozkir, Hilmi; Gurkan, Hakan; Duymaz, Julide; Demir, Ahmet Muzaffer; Pamuk, Omer Nuri[Abstract Not Available]
