A weak association of HLA-B*2702 with Behçet’s disease

Gül, Ahmet; Uyar, Fatma; İnanç, Murat; Öçal, Lale; Barrett, Jennifer; Aral, Orhan; Koniçe, M; Saruhan‐Direskeneli, Güher

doi:10.1038/sj.gene.6363863

Cited by 58 publications

(12 citation statements)

References 33 publications

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“…Associations between other HLA-B types and BD have been reported (8)(9)(10), as have associations between BD and both HLA-A and HLA-C alleles (2,3,(14)(15)(16)(17). In our study, we observed that HLA-B*15, -B*27, and -B*57 were independent susceptibility alleles for BD, consistent with earlier reports.…”

Section: Discussionsupporting

confidence: 82%

“…This evidence begins in the HLA-B locus, where associations between BD and several alleles in addition to HLA-B*51 have been reported (8)(9)(10). It also has been argued that variants in or around MHC class I polypeptide-related sequence A (MICA), the centromeric neighbor of HLA-B that encodes the MHC-I chain-related sequence A, contribute to BD susceptibility (11).…”

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confidence: 99%

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Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity

Ombrello

Kirino

Bakker

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

125

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The HLA protein, HLA-B*51, encoded by HLA-B in MHC, is the strongest known genetic risk factor for Behçet disease (BD). Associations between BD and other factors within the MHC have been reported also, although strong regional linkage disequilibrium complicates their confident disentanglement from HLA-B*51. In the current study, we examined a combination of directly obtained and imputed MHC-region SNPs, directly obtained HLA-B locus types, and imputed classical HLA types with their corresponding polymorphic amino acid residues for association with BD in 1,190 cases and 1,257 controls. SNP mapping with logistic regression of the MHC identified the HLA-B/MICA region and the region between HLA-F and HLA-A as independently associated with BD (P < 1.7 × 10 −8 ). HLA-B*51, -A*03, -B*15, -B*27, -B*49, -B*57, and -A*26 each contributed independently to BD risk. We directly examined rs116799036, a noncoding SNP upstream of HLA-B that was recently suggested to underlie the association of HLA-B*51 with BD, but we were unable to replicate that finding in our collection. Instead, we mapped the BD association to seven MHC class I (MHC-I) amino acid residues, including anchor residues that critically define the selection and binding of peptides to MHC-I molecules, residues known to influence MHC-Ikiller immunoglobulin-like receptor interactions, and a residue located in the signal peptide of HLA-B. The locations of these variants collectively implicate MHC-I peptide binding in the pathophysiology of BD. Furthermore, several lines of evidence suggest a role for altered regulation of cellular cytotoxicity in BD pathogenesis.HLA imputation | autoinflammation | antigen presentation | killer immunoglobulin-like receptors | natural killer cells

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity

Ombrello

Kirino

Bakker

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

125

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“…For rare studies reporting results for both HLA–B5 and HLA–B51 genotypes (4,25,42,80,93), only the latter data were used for all analyses. The classification criteria used were: the International Study Group for Behçet’s Disease (97), n = 36; (19–22,26, 28,32,34,43,44,48,50 –55,57,63,64,67,68,72,74 –76,78,81, 87– 89,91,92,95); 1974/1987 revised JBDRC (96,98), n = 16 (4,24,29,31,33,45,47,60–62,70,71,79,84,85,94); O’Duffy (99), n = 6 (25,27,40,66,69,93); Mason and Barnes (100), n = 4 (23,39,42,56); Cheng and Zhang (101), n = 1 (82); and multiple sets, n = 5 (30,38,46,58,73). For 12 study populations, no statements were made with respect to the criteria used to define BD cases (35–37,49,59,65,77,80,83,86,90).…”

Section: Resultsmentioning

confidence: 99%

HLA–B51/B5 and the risk of Behçet's disease: A systematic review and meta‐analysis of case–control genetic association studies

Menthon

LaValley

Maldini

et al. 2009

Arthritis & Rheumatism

409

231

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Objective To quantify by meta-analysis the genetic effect of the HLA–B5 or HLA–B51 (HLA–B51/B5) allele on the risk of developing Behçet’s disease (BD) and to look for potential effect modifiers. Methods Relevant studies were identified using the PubMed Medline database and manual searches of the literature. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by using the random-effects model. Subgroup meta-analyses and meta-regression analyses were undertaken to investigate the effects of selected study-level parameters on the pooled OR. Heterogeneity was assessed using the I2 statistic. Pooled results were used to calculate population-attributable risks (PAR) for BD in relationship to HLA–B51/B5. Results A total of 4,800 patients with BD and 16,289 controls from 78 independent studies (published 1975–2007) were selected. The pooled OR of HLA–B51/B5 allele carriers to develop BD compared with noncarriers was 5.78 (95% CI 5.00–6.67), with moderate between-study heterogeneity (I2 = 61%). The subgroup analyses stratifying studies by geographic locations (Eastern Asia, Middle East/North Africa, Southern Europe, Northern/Eastern Europe) yielded consistent OR ranges (5.31–7.20), with I2 ranges of 52–70%. Univariate random-effects meta-regression indicated the percentage of male BD cases (P = 0.008) as a source of heterogeneity. The PAR within the various geographic areas were estimated at 32–52%. Conclusion The strength of the association between BD and HLA–B51/B5, and its consistency across populations of various ethnicities, lends further support to this allele being a primary and causal risk determinant for BD. Variations according to sex support an interaction of this allele with BD characteristics.

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“…The etiology of BD is unknown and BD is seen most frequently among Turkish, Israeli and Japanese populations. It has been claimed that immunologic abnormalities triggered by microbial agents or environmental factors in genetically susceptible individuals play an important role in the development of this disease [2] . Vascular injuries, hyperfunction of neutrophils, and autoimmune responses are also signifi cant characteristics of BD [3] , but the clinical features of BD differ from those of classic autoimmune diseases [4] .…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-Converting Enzyme I/D Polymorphism in Behçet’s Disease

Turgut¹,

Turgut²,

Atalay

et al. 2005

Med Princ Pract

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Objective: To investigate a potential relationship between I/D polymorphism within intron 16 of the angiotensin-converting enzyme (ACE) gene located on human chromosome 17 and Behçet’s disease. Materials and Methods: Genomic DNA was obtained from 35 Turkish patients diagnosed with Behçet’s disease according to the International Study Group criteria and 150 healthy individuals. Polymerase chain reaction was used to detect the presence of I and D (insertion and deletion) alleles in intron 16 of the ACE gene in these DNA samples. Results: We found differences in ACE I/D polymorphism between Behçet’s disease and healthy controls (χ² = 4.61, d.f. = 1, p = 0.044). In Behçet’s disease patients, the D allele frequency was 84.3% and I allele frequency 15.7%. Conclusion: An association between Behçet’s disease and ACE polymorphism may provide a useful basis for future molecular studies and therapeutic approaches in this complex disease.

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A weak association of HLA-B*2702 with Behçet’s disease

Abstract: This study aimed to analyse the association of HLA-B alleles other than -B51 with Behçet's disease (BD).

Cited by 58 publications

References 33 publications

Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity

Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity

HLA–B51/B5 and the risk of Behçet's disease: A systematic review and meta‐analysis of case–control genetic association studies

Angiotensin-Converting Enzyme I/D Polymorphism in Behçet’s Disease

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