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

Abstract

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.

HLA-B51 subtypes in Turkish patients with Behçet's disease and their correlation with clinical manifestations

“…This finding is consistent with earlier studies on HLA-B5/B51 positivity. (de Menthon et al, 2009;Maldini et al, 2012).…”

“…Although the pathogenesis is not exactly known, it is believed to be triggered by microbial or environmental factors, with a genetic predisposition. In many ethnic groups that settled along the ancient Silk Road, a significant relationship is detected between BD and HLA-B51positivity (Kaya et al, 2002;Kötter et al, 2004;de Menthon et al, 2009;Song and Kang, 2012;Hughes et al, 2013;Houman et al, 2013).…”

Role of genetics in pediatric rheumatology

“…Although many cases of BS are sporadic, familial aggregation is observed with varing frequencies in different populations (more frequenct in juvenile patients) (42,43). The strongest genetic factor associated with the risk of Behçet syndrome is the HLA-B5/B51 allele carrier state, which is observed more frequently in familial cases compared with sporadic BS (44,45). In a meta-analysis that comprised 4 800 patients with BS and 16 289 controls, the HLA-B51/B5 frequency was found as 57.2% in patients with BS, and 18.1% in the controls (OR 5.78, 95% CI: [5.00-6.67]) (45).…”

“…The strongest genetic factor associated with the risk of Behçet syndrome is the HLA-B5/B51 allele carrier state, which is observed more frequently in familial cases compared with sporadic BS (44,45). In a meta-analysis that comprised 4 800 patients with BS and 16 289 controls, the HLA-B51/B5 frequency was found as 57.2% in patients with BS, and 18.1% in the controls (OR 5.78, 95% CI: [5.00-6.67]) (45). In another study, it was shown that the HLA-B*5101 variant had a strong relation with BS, and the MICA-A6 allele was reported to increase predisposition to BS (46 …”

A meta-analysis of the association between Behçet's disease and MICA-A6

“…A number of previous studies have indicated that BD is associated with environmental risk factors such as infectious agents, which are likely involved in the susceptibility to the disease (3). The HLA-B51 allele polymorphism has been associated with the pathogenesis of BD (4). Furthermore, major histocompatibility complex (MHC) class I chain related A (MICA) is a functional gene located between the HLA-B and tumor necrosis factor genes on the short arm of human chromosome (5).…”