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Meta-Analysis
. 2009 Oct 15;61(10):1287-96.
doi: 10.1002/art.24642.

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

Mathilde de Menthon  1 , Michael P Lavalley, Carla Maldini, Loïc Guillevin, Alfred Mahr
Affiliations
Meta-Analysis

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

Mathilde de Menthon et al. Arthritis Rheum. .

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.

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Figures

Figure 1
Figure 1
Flow chart of studies identified through the systematic review of the literature. BD = Behçet’s disease.
Figure 2
Figure 2
Forest plot of results of published studies on the association between HLA–B51/B5 and Behçet’s disease (BD) (listed chronologically). Odds ratios (ORs) for the risk of HLA–B51/B5 allele carriers to develop BD compared with noncarriers. The dashed vertical line indicates the pooled value for the entire population considered. *See Materials and Methods for a list of other criteria applied. 95% CI = 95% confidence interval; E = Eastern; Serol. = serologic; JBDRC = Japanese Behçet’s Disease Research Committee; N = North; M = Middle; NR = not reported; S = Southern; ISG = International Study Group; Molec. = molecular.
Figure 3
Figure 3
Funnel plot for publication bias. The dashed vertical line indicates the pooled estimate. Precision was assessed by the inverse variance method.
See this image and copyright information in PMC

References

    1. Kaklamani VG, Vaiopoulos G, Kaklamanis PG. Behçet’s disease. Semin Arthritis Rheum. 1998;27:197–217. - PubMed
    1. Sakane T, Takeno M, Suzuki N, Inaba G. Behçet’s disease. N Engl J Med. 1999;341:1284–91. - PubMed
    1. Ono S, Aoki K, Sugiura S, Nakayama E, Itakura K. HL-A5 and Behçet’s disease [letter] Lancet. 1973;2:1383–4. - PubMed
    1. Ohno S, Ohguchi M, Hirose S, Matsuda H, Wakisaka A, Aizawa M. Close association of HLA-Bw51 with Behçet’s disease. Arch Ophthalmol. 1982;100:1455–8. - PubMed
    1. Du KM, Ji Y, Xie JH, Fu M, Sun Y, Jin Y, et al. HLA-A, -B, -DR haplotype frequencies from DNA typing data of 26,266 Chinese bone marrow donors. Hum Immunol. 2007;68:854–66. - PubMed

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