HLA-B51/B5 and the Risk of Behcet's Disease: A Systematic Review and Meta-Analysis of Case-Control Genetic Association Studies

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 Behc, et'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 I-2 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 (I-2 = 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 I-2 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.