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F Fayyad

Publications and source records attributed to F Fayyad.

6 recordsLinked to original sources
PubMed2001

Microsatellite mapping of a susceptible locus within the HLA region for Behçet's disease using Jordanian patients.

Behçet's disease (BD) has been established to be associated with HLA-B51. However, it has not been revealed whether the HLA-B51 gene itself or another gene located near the HLA-B gene is directly involved in the pathogenesis of BD. Previously, using Japanese BD patients, our group has narrowed down a BD-causative gene to 46 kb between the MICA and HLA-B genes by means of fine mapping analysis with eight microsatellite markers distributed within a 1100 kb segment around the HLA-B gene. To know whether this mapping result is generally observed in BD of another population we have investigated repeat polymorphisms of the same microsatellite markers in Jordanian BD patients. Furthermore, we have evaluated these data by Mantel-Haenzel stratified analysis to find out a primarily associated locus for BD. As a result, HLA-B51 was found to be the most strongly and primarily associated marker. This result suggests that the pathogenic gene of BD is HLA-B51 itself, but unlikely to be other genes located in the vicinity of HLA-B.

Adolescent↗
PubMed2000

Intercellular adhesion molecule-1 gene polymorphisms in Behçet's disease.

Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been implicated in the susceptibility to inflammatory diseases, including multiple sclerosis and inflammatory bowel disease. The expression of both soluble and tissue ICAM-1 is increased in Behçet's disease (BD) but the contribution of ICAM-1 gene polymorphisms to this disease remains unknown. Associations with BD have been reported for genes within the MHC, including HLA-B51, TNF and MICA, but the role of non-MHC genes in BD remains largely unexplored. We have investigated the frequency of the R/G 241 and K/E 469 ICAM-1 gene polymorphisms in 83 patients with BD disease and 103 healthy controls, all of Palestinian and Jordanian descent, and demonstrated an association between BD and the ICAM-1 E469 allele (Pc = 0.046, OR = 2.1). Among patients, no association was found between the presence of ocular disease and ICAM-1 polymorphisms. While the functional correlate of this polymorphism remains unclear, this finding indicates that a genetic polymorphism in the ICAM-1 gene domain, which is independent of the MHC, may contribute to disease.

Behcet Syndrome↗
PubMed1999

Factor V Leiden mutation is associated with ocular involvement in Behçet disease.

PURPOSE: Behçet disease is a systemic disease of young adults characterized by venous occlusion in both the deep venous and retinal circulations. In severe ocular disease, blindness may occur despite immunosuppressive treatment. The most common inherited risk factor for the development of idiopathic venous thrombosis is the presence of the Factor V (FV Leiden) mutation, which confers resistance to activated protein C. The association of FV Leiden with Behçet disease has been reported, but its influence on ocular disease is not known. We therefore investigated the prevalence of this mutation in patients with Behçet disease to determine its contribution to the presence and severity of ocular disease. METHODS: One hundred and six Middle Eastern patients satisfying international criteria, and 120 healthy control subjects without a history of venous thrombosis were included in the study, and patients underwent standard examination by two ophthalmologists with an interest in Behçet disease. Genomic DNA was extracted from peripheral blood leukocytes and screened for the FV Leiden mutation with the polymerase chain reaction method with sequence-specific primers (PCR-SSP). RESULTS: FV Leiden was detected in 19% (23/120) of the control population compared with 27% (29/106) of all patients with Behçet disease (P = .13). However, among patients with Behçet disease who had ocular disease (75/106), the prevalence of FV Leiden was significantly higher (32%) than it was in control subjects (P = .04). Furthermore, ocular patients with Behçet disease in whom retinal occlusive disease was observed (25/75) had the highest expression of FV Leiden (44%). CONCLUSIONS: These data suggest that FV Leiden may be an additional risk factor for the development of ocular disease and, in particular, retinal vaso-occlusion, and it may contribute to the poor visual outcome in these patients.

Adolescent↗
PubMed1999

HLA and tumour necrosis factor (TNF) polymorphisms in ocular Behçet's disease.

The role of HLA-B*51 and other major histocompatibility complex (MHC) genes in Behçet's disease (BD) remains unknown. We have performed HLA and tumour necrosis factor (TNF) polymorphism analysis in BD and evaluated their contribution to ocular disease. In this study, 102 patients and 115 controls of Middle Eastern descent were investigated by HLA and B*51 subtyping using novel primers, and by LT alpha NCo 1 and TNF 308 promoter polymorphism analysis. The frequency of the HLA-B*51 family of alleles was raised in patients compared to controls (66% vs. 15%, Pc=2.5x10(-12), OR=10.9). The odds ratio (OR) of this group of alleles for subgroups of patients was as follows: non-ocular patients 7.8, all ocular patients 12.6, blind patients >22. HLA-B*51 subtyping detected B*5101, 07, 08 and 09 alleles, with a similar frequency among patients and controls. HLA-Cw*1602 was associated with B*5108, but was not an independent risk factor for disease. The LT alpha (TNFB*2) allele was associated with HLA-B*51 among patients and the frequency of this allele was significantly higher among completely blind patients compared to both non-ocular patients (P=0.048, OR >3.6) and to healthy controls (P=0.022, OR >4.3). The rare TNF-2 polymorphism at the TNF -308 promoter position was associated with HLA-B*50 (not B*51), and was not associated with BD. Thus, in this population the HLA*B51 family of alleles is a strong risk factor for BD, and in particular the development of ocular disease. HLA-B*51 subtyping did not define new markers for BD. A primary role for TNF gne polymorphisms in BD was not identified, but co-expression of the TNFB*2 allele with HLA-B*51 may contribute to severity of ocular disease.

Adolescent↗
PubMedDate not supplied

CARD15 polymorphisms in Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a chronic multi-system inflammatory disorder of unknown aetiology, which shares many features of the inflammatory bowel diseases (IBDs). CARD15 has recently been identified as the first susceptibility gene in Crohn's disease (CD). OBJECTIVE: Given certain clinical and pathological similarities between CD and BD, and recent evidence of linkage of BD to the CARD15 genomic region, the aim of this study was to investigate the role of CARD15 variants in determining susceptibility to BD. METHODS: We studied 374 BD patients from three ethnically homogeneous cohorts (white English, Turkish, and Middle Eastern Arabs of Palestinian and Jordanian descent). Mutation detection of CARD15 was performed by direct sequencing in a subset of patients from each group and the identified variants were genotyped in the complete cohorts. Case-control analyses were carried out with additional stratification by the BD-associated allele, HLA-B*51. RESULTS: Mutation detection identified six previously described CARD15 polymorphisms at a frequency of > 3%. Additionally, two of the three CD-associated polymorphisms were present, but at low frequency. The frequency of haplotypes, constructed from nine genotyped polymorphisms, demonstrated significant variation between different ethnic groups. However, case-control analyses demonstrated no association between the CARD15 polymorphisms and susceptibility to BD, irrespective of HLA-B*51 status. CONCLUSION: CARD15 variant alleles are not associated with susceptibility to BD. Other shared loci, currently under investigation, may determine susceptibility to both CD and BD.

Arabs↗