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OBJECTIVE: The etiology of Behçet's disease is unknown; however, familial aggregation studies indicate a strong genetic background and a complex inheritance model. Association of HLA-B51 with Behçet's disease is regarded as being the strongest evidence of genetic contribution described to date. A low rate of recombination was observed within the telomeric end of the major histocompatibility complex up to the HFE gene, which causes hereditary hemochromatosis. We therefore hypothesized that the telomere of 6p may harbor a susceptibility gene for Behçet's disease. METHODS: A series of 28 multicase families of Turkish origin was ascertained, and 78 of the 183 available family members were diagnosed as having Behçet's disease. For the analysis of the telomeric region adjacent to HLA-B, we used a panel of 20 highly polymorphic microsatellite markers between D6S273 and D6S470, covering a region of approximately 36 cM. RESULTS: Multipoint nonparametric linkage analysis using GeneHunter 2.0 software revealed a broad peak of linkage, with the highest Z score of 4.11 at position D6S285, which is approximately 17 cM telomeric to HLA-B. CONCLUSION: This significant linkage finding may indicate a second susceptibility locus in the telomere of chromosome 6p. Identification of this putative susceptibility gene could help to further understand the pathogenesis of Behçet's disease.

Original publication

DOI

10.1002/1529-0131(200111)44:11<2693::aid-art449>3.0.co;2-m

Type

Journal article

Journal

Arthritis and rheumatism

Publication Date

11/2001

Volume

44

Pages

2693 - 2696

Addresses

Department of Internal Medicine, Istanbul Faculty of Medicine, University of Istanbul, Turkey. agul@istanbul.edu.tr

Keywords

Chromosomes, Human, Pair 6, Humans, Behcet Syndrome, Genetic Predisposition to Disease, DNA, HLA-B Antigens, Chromosome Mapping, Microsatellite Repeats, Lod Score, Turkey, Female, Male