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51. Association of TRPM Channel Gene Polymorphisms with Systemic Sclerosis

Author

Oztuzcu, S., Onat, A. M., Pehlivan, Y., Alibaz-Oner, F., Donmez, S., Cetin, G. Y., Yolbas, S., ibrahim bozgeyik, Yilmaz, N., Ozgen, M., Cagatay, Y., Kisacik, B., Koca, S. S., Pamuk, O. N., Sayarlioglu, M., Direskeneli, H., and Demiryurek, A. T.

Abstract

Background/Aim: Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc. Materials and Methods: A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system. Results: There were marked increases in the CC genotype (94.7% vs 81.8%, p

Published
2015

52. Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an

Author

Renauer, PA, Saruhan-Direskeneli, G, Coit, P, Adler, A, Aksu, K, Keser, G, Alibaz-Oner, F, Aydin, SZ, Kamali, S, Inanc, M, Carette, S, Cuthbertson, D, Hoffman, GS, Akar, S, Onen, F, Akkoc, N, Khalidi, NA, Koening, C, Karadag, O, Kiraz, S, Langford, CA, Maksimowicz-McKinnon, K, McAlear, CA, Ozbalkan, Z, Ates, A, Karaaslan, Y, Duzgun, N, Monach, PA, Ozer, HTE, Erken, E, Ozturk, MA, Yazici, A, Cefle, A, Onat, AM, Kisacik, B, Pagnoux, C, Kasifoglu, T, Seyahi, E, Fresko, I, Seo, P, Sreih, AG, Warrington, KJ, Ytterberg, SR, Cobankara, V, Cunninghame-Graham, DS, Vyse, TJ, Pamuk, ON, Tunc, SE, Dalkilic, E, Bicakcigil, M, Yentur, SP, Wren, JD, Merkel, PA, Direskeneli, H, and Sawalha, AH

Abstract

Objective. Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. Methods. Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results. We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 x 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 x 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 x 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 x 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 x 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Conclusion. Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Published
2015

53. Behçet disease with vascular involvement: Effects of different therapeutic regimens on the incidence of new relapses

Author

Alibaz-Oner F, Karadeniz A, Ylmaz S, Balkarl A, Kimyon G, Yazc A, Çnar M, Yldz F, Bilge ŞY, Bilgin E, Coskun BN, Omma A, Çetin GY, Çağatay Y, Karaaslan Y, Sayarlioğlu M, Pehlivan Y, Kalyoncu U, Karadağ Ö, Kaşifoğlu T, Erken E, Pay S, Çefle A, Kisacik B, Onat AM, Çobankara V, and Direskeneli H

Subjects
Adult, Male, Vasculitis, corticosteroid, demography, epistaxis, recurrent disease, retrospective study, anticoagulant agent, gastrointestinal hemorrhage, methotrexate, Article, Recurrence, follow up, Humans, human, vascular Behcet disease, Retrospective Studies, relapse, azathioprine, physician, treatment duration, anticoagulant therapy, low molecular weight heparin, Behcet Syndrome, hematoma, immunosuppressive treatment, vascular disease, immunosuppressive agent, bleeding, Behcet Syndrome/*pathology/*therapy, Female, Follow-Up Studies, Vasculitis/pathology/therapy, major clinical study, alpha interferon, clinical feature, warfarin, female, priority journal, cyclophosphamide, pathology, infliximab, Behcet disease, recurrence risk
Abstract

Vascular involvement is one of the major causes of mortality and morbidity in Behcet disease (BD). There are no controlled studies for the management of vascular BD (VBD), and according to the EULAR recommendations, only immunosuppressive (IS) agents are recommended. In this study, we aimed to investigate the therapeutic approaches chosen by Turkish physicians during the initial event and relapses of VBD and the association of different treatment options with the relapses retrospectively. Patients with BD (n-936, female/male: 347/589, mean age: 37.6 ± 10.8) classified according to ISG criteria from 15 rheumatology centers in Turkey were included. The demographic data, clinical characteristics of the first vascular event and relapses, treatment protocols, and data about complications were acquired. VBD was observed in 27.7% (n - 260) of the patients during followup. In 57.3% of the VBD patients, vascular involvement was the presenting sign of the disease. After the first vascular event, ISs were given to 88.8% and AC treatment to 59.8% of the patients. Median duration of AC treatment was 13 months (1-204) and ISs, 22 months (1-204). Minor hemorrhage related to AC treatment was observed in 7 (4.7%) patients. Asecond vascular event developed in 32.9% (n=86) of the patients. The vascular relapse rate was similar between patients taking only ISs and AC plus IS treatments after the first vascular event (29.1% vs 22.4%, P=0.28) and was significantly higher in group taking only ACs than taking only ISs (91.6% vs 29.1%, P

Published
2015

54. Therapeutic Regimens on the Incidence of New Relapses

Author

Alibaz-Oner, F, Karadeniz, A, Yilmaz, S, Balkarli, A, Kimyon, G, Yazici, A, Cinar, M, Yildiz, F, Bilge, SY, Bilgin, E, Coskun, BN, Omma, A, Cetin, GY, Cagatay, Y, Karaaslan, Y, Sayarlioglu, M, Pehlivan, Y, Kalyoncu, U, Karadag, O, Kasifoglu, T, Erken, E, Pay, S, Cefle, A, Kisacik, B, Onat, AM, Cobankara, V, and Direskeneli, H

Abstract

Vascular involvement is one of the major causes of mortality and morbidity in Behcet disease (BD). There are no controlled studies for the management of vascular BD (VBD), and according to the EULAR recommendations, only immunosuppressive (IS) agents are recommended. In this study, we aimed to investigate the therapeutic approaches chosen by Turkish physicians during the initial event and relapses of VBD and the association of different treatment options with the relapses retrospectively. Patients with BD (n = 936, female/male: 347/589, mean age: 37.6 +/- 10.8) classified according to ISG criteria from 15 rheumatology centers in Turkey were included. The demographic data, clinical characteristics of the first vascular event and relapses, treatment protocols, and data about complications were acquired.

Published
2015

60. Arteritis

Author

Saruhan-Direskeneli, G, Hughes, T, Aksu, K, Keser, G, Coit, P, Aydin, SZ, Alibaz-Oner, F, Kamali, S, Inanc, M, Carette, S, Hoffman, GS, Akar, S, Onen, F, Akkoc, N, Khalidi, NA, Koening, C, Karadag, O, Kiraz, S, Langford, CA, McAlear, CA, Ozbalkan, Z, Ates, A, Karaaslan, Y, Maksimowicz-McKinnon, K, Monach, PA, Ozer, HT, Seyahi, E, Fresko, I, Cefle, A, Seo, P, Warrington, KJ, Ozturk, MA, Ytterberg, SR, Cobankara, V, Onat, AM, Guthridge, JM, James, JA, Tunc, E, Duzgun, N, Bicakcigil, M, Yentur, SP, Merkel, PA, Direskeneli, H, and Sawalha, AH

Abstract

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped similar to 200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 x 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 x 10(-9); and rs189754752, OR = 2.47, p = 4.22 x 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 x 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 x 10(-8)).

Published
2013

72. FRI0265 Validation of New 2012 EULAR/ACR Clinical Classification Criteria for Polymyalgia Rheumatica: Comparison with the Previous Criteria in a Prospective Multi-Center Study

Author

Ozen, G., primary, Bas, S., additional, Unal, A.U., additional, Kimyon, G., additional, Onat, A.M., additional, Murat, S., additional, Keskin, H., additional, Sahin, A., additional, Can, M., additional, Mengi, A., additional, Yilmaz, S., additional, Balkarli, A., additional, Cobankara, V., additional, Pamuk, O.N., additional, Cagatay, Y., additional, Bayindir, O., additional, Aksu, K., additional, Alibaz-Oner, F., additional, Gok, K., additional, Senel, S., additional, Yilmaz, N., additional, Yildirim-Cetin, G., additional, Akyol, L., additional, Sayarlioglu, M., additional, Yagci, I., additional, Atagunduz, P., additional, Aydin, S.Z., additional, Inanc, N., additional, and Direskeneli, H., additional

Published
2015
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74. Activation of the JAK/STAT pathway in Behcet’s disease

Author

Tulunay, A, primary, Dozmorov, M G, additional, Ture-Ozdemir, F, additional, Yilmaz, V, additional, Eksioglu-Demiralp, E, additional, Alibaz-Oner, F, additional, Ozen, G, additional, Wren, J D, additional, Saruhan-Direskeneli, G, additional, Sawalha, A H, additional, and Direskeneli, H, additional

Published
2014
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79. OP0234 Effects of Anticoagulant Treatment on the Incidence of New Vascular Events in Patients with Behcet's Disease with Vascular Involvement

Author

Alibaz-Oner, F., primary, Karadeniz, A., additional, Yilmaz, S., additional, Balkarlı, A., additional, Cobankara, V., additional, Yazıcı, A., additional, Cefle, A., additional, Kimyon, G., additional, Kisacik, B., additional, Onat, A.M., additional, Yildiz, F., additional, Erken, E., additional, Bilge, S.Y., additional, Kasifoglu, T., additional, Yildirim Cetin, G., additional, Sayarlıoglu, M., additional, and Direskeneli, H., additional

Published
2014
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90. SAT0222 Investigating the Association Between Rho-Kinase 1 (Rock1) Gene Polymorphisms and Systemic Sclerosis

Author

Pehlivan, Y., primary, Oztuzcu, S., additional, Donmez, S., additional, Alibaz-Oner, F., additional, Yildirim Cetin, G., additional, Yolbas, S., additional, Bozgeyik, I., additional, Yilmaz, N., additional, Ozgen, M., additional, Kisacik, B., additional, Pamuk, O. N., additional, Sayarlioglu, M., additional, Direskeneli, H., additional, Tuncay Demiryurek, A., additional, and Mesut Onat, A., additional

Published
2013
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