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      Association between polymorphisms of FCRL3, a non-HLA gene, and Behçet’s disease in a Chinese population with ophthalmic manifestations

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          Abstract

          Purpose

          Studies have shown a strong association of human leukocyte antigens-B51 ( HLA-B51) with Behçet’s disease (BD). However, little is known about the association of non- HLA genes with BD. The polymorphisms of the Fc receptor-like 3 gene ( FCRL3), −169C/T, −110A/G, +358C/G, and +1381A/G, have been reported to be associated with several autoimmune diseases. This study was designed to determine whether the polymorphisms of FCRL3 were associated with susceptibility to BD in a Chinese population mainly with ocular involvement.

          Methods

          A case-control study was performed in 245 Chinese BD patients and 289 controls. Four single nucleotide polymorphisms (SNPs; −169C/T, −110A/G, +358C/G, and +1381A/G) in FCRL3 were detected using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP). HLA-B51 genotyping was performed by the PCR sequence specific primers method as described previously.

          Results

          The results showed a significantly higher frequency of the G allele at the −110 site in BD patients compared with that in controls (corrected p=0.044, 75.3% versus 67.5%, χ 2=7.72). Haplotype CGCG frequency was significantly higher in patients than in controls (corrected p=0.0096) whereas haplotype TACG frequency was significantly lower in patients compared with controls (corrected p=0.032). There was no relationship between clinical signs and FCRL3 polymorphisms. No significant difference was observed between patients and controls after HLA-B51 stratification concerning the four SNPs.

          Conclusions

          Our study suggests that the −110 G allele and the haplotype CGCG of FCRL3 are positively associated with BD in a Chinese population and that the haplotype ATCG might be a protective haplotype for BD.

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          Most cited references25

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          Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP).

          We have developed a single DNA typing method which uses 144 sequence-specific primer (SSP) reactions to simultaneously detect all known HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 and DQB1 specificities in an allele specific or group specific manner using the same method, reagents, PCR parameters and protocols for all loci. The results from this integrated class I & II method can be visualized on a single photographic or electronic image and hence is described as "Phototyping". Phototyping has an overall resolution greater than or equivalent to good serology and results can be obtained in under 3 hours making the method suitable for genotyping potential cadaver donor peripheral blood without serological backup. This in turn produces the potential for reducing cold ischaemia times in renal transplantation as well as the application of prospective matching to cardiac and liver transplantation. The method has capacity to detect new alleles, for example, novel amplification patterns suggestive of 4 new HLA-B alleles have been detected. The Phototyping set has been used as the sole method of HLA typing for over 1010 individuals. Phototyping is not problem-free; deviations from the standard protocol, poor quality DNA and unsuitable PCR machines can result in individual PCR failures or in incorrect assignment of antigens. Approximately 5% of genotypes were repeated (either partially or fully) because of incomplete or equivocal results.
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            Clinical features of chinese patients with Behçet's disease.

            To characterize the clinical features of Behçet's disease in Chinese patients. Retrospective noncomparative case series. Seven hundred seventy-five eyes of 437 patients with Behçet's disease initially examined from August, 1995, through June, 2006. The history, demographic parameters, and clinical findings of all consecutive Behçet's patients referred to the uveitis study center of Sun Yat-sen University were reviewed. Laser flare-cell photometry (LFCM), fundus fluorescein angiography (FFA), optical coherence tomography (OCT), ultrasound biomicroscopy (UBM), and B-scan ultrasonography were performed in certain cases. Most patients were treated by immunosuppressive agents combined with oral corticosteroids. Patient demographics, clinical presentation, and auxiliary examination findings. Four hundred thirty-seven patients were diagnosed with Behçet's disease. There were 319 male and 118 female patients. Panuveitis was the most common type of uveitis in both genders, although anterior uveitis was seen more frequently in females. Retinal vasculitis, vitreitis, and retinitis were the most common ocular manifestations in these patients. Cataract and macular edema were the most common complications. Oral aphthae were the most frequent extraocular manifestation, followed by dermatologic lesions, and genital ulcers. The results of FFA, OCT, B-scan ultrasonography, LFCM, and UBM generally were in accordance with or comparable with clinical observations. At the final visit, uveitis was well controlled in 86.2% of patients. However, 20.4% of eyes became legally blind despite aggressive treatment. Kaplan-Meier analysis estimated the risk of losing useful vision (0.05) at 5 and 10 years for males and females as 29% versus 6% and 65% versus 33%, respectively. Behçet's disease in Chinese patients mainly manifests as nongranulomatous uveitis frequently associated with oral aphthae and dermatologic lesions. Fundus fluorescein angiography, B-scan ultrasonography, LFCM, UBM, and OCT may provide much information about pathophysiologic hallmarks of Behçet's disease. A combination of corticosteroids with other immunosuppressive agents is effective for most patients with Behçet's disease. Males had a more severe course and were at higher risk for losing vision than females.
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              NF-kappaB activation and inhibition: a review.

              Among transcriptional regulatory proteins described, NF-kappaB seems particularly important in modulating the expression of immunoregulatory genes relevant in critical illness, inflammatory diseases, apoptosis, and cancer. In particular, NF-kappaB plays a central role in regulating the transcription of cytokines, adhesion molecules, and other mediators. The biochemical basis by which diverse stimuli converge to activate or intervene this family of transcription factors is still largely unknown. The NF-kappaB transcription factor family represents an important group of regulators of a broad range of genes involved in cellular responses to inflammatory and other kinds of signals. Knockout mouse studies have also revealed a key role for this family in broad physiological processes, including immune function and metabolism. Overall, specificity seems to exist in the role of each transcriptional complex in gene transcription and physiological function. Each NF-kappaB complex displays distinct affinities for the different DNA-binding sites present in the promoters of NF-kappaB-regulated genes, and this may contribute to some of the specificity exhibited. The identification of specific components of the NF-kappaB signal transduction pathway provides an opportunity to define mechanisms at the biochemical level by which specific members of the NF-kappaB family are activated. Furthermore, this may identify specific targets for selective inhibition or promotion of NF-kappaB functions. Further studies will be required to elucidate mechanisms regulating specificity and selectivity of NF-kappaB function, as well as its role in different diseases, prior to potential clinical application.
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                Author and article information

                Journal
                Mol Vis
                MV
                Molecular Vision
                Molecular Vision
                1090-0535
                2008
                28 November 2008
                : 14
                : 2136-2142
                Affiliations
                [1 ]First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
                [2 ]Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P.R. China
                [3 ]Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, Maastricht, the Netherlands
                Author notes

                Dr. Li and Dr. Zhao contributed equally to this work.

                Correspondence to: Professor Peizeng Yang, MD, Ph.D., First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, P.R. China, 400016; Phone: 8623 89012851; FAX: 862389012851; email: peizengy@ 123456126.com
                Article
                250 2008MOLVIS0336
                2592528
                19050767
                3e9d0c7a-41a1-49b9-972d-33163e166164
                Copyright @ 2008

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 October 2008
                : 19 November 2008
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                Research Article
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                Vision sciences
                Vision sciences

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