Association between HLA-DRB1 polymorphisms and pemphigus vulgaris: a meta-analysis

BACKGROUND Several studies have reported that HLA-DRB1 may be correlated with pemphigus vulgaris (PV), but most have been based on small samples and the results remain inconsistent and unclear. OBJECTIVES To investigate the correlation between DRB1 and PV by a meta-analysis of case-control/nonfamily studies. METHODS PubMed, Wiley Online Library, ScienceDirect, Google Scholar, Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang databases were searched for studies including: (i) 'pemphigus'; and (ii) 'human leukocyte antigen', 'HLA', 'major histocompatibility complex', 'MHC' or 'DRB1'. Eighteen selected studies were used in meta-analyses to evaluate DRB1 alleles and phenotypes by calculating the respective odds ratios (ORs) and 95% confidence intervals (CIs). Stratified meta-analyses and meta-regression analysis were also conducted. RESULTS The frequencies of three genotypes (allele and phenotype, respectively) were significantly increased in PV: DRB1*04 [P-value for comparability (Pc) < 0.00001, OR 3.61, 95% CI 2.28-5.71; Pc = 0.0002, OR 4.14, 95% CI 1.98-8.65], DRB1*08 (Pc = 0.03, OR 2.25, 95% CI 1.07-4.70; Pc = 0.0003, OR 2.46, 95% CI 1.51-4.01) and DRB1*14 (Pc < 0.00001, OR 6.47, 95% CI 4.52-9.26; Pc < 0.00001, OR 9.68, 95% CI 4.47-20.98). Three others (allele and phenotype, respectively) were significantly decreased in PV: DRB1*03 (Pc < 0.00001, OR 0.28, 95% CI 0.19-0.41; Pc = 0.0001, OR 0.25, 95% CI 0.12-0.51), DRB1*07 (Pc = 0.004, OR 0.45, 95% CI 0.26-0.78; Pc = 0.0002, OR 0.27, 95% CI 0.14-0.54) and DRB1*15 (Pc = 0.001, OR 0.35, 95% CI 0.18-0.66; Pc = 0.002, OR 0.32, 95% CI 0.16-0.65). Ethnicity partially explained the heterogeneity of DRB1*07, DRB1*08 and DRB1*14 phenotypes. CONCLUSIONS Our findings suggest that DRB1*04, DRB1*08 and DRB1*14 are statistically significant susceptibility factors for PV. Conversely, DRB1*03, DRB1*07 and DRB1*15 may be negatively associated with PV. Specific HLA-DRB1 types may influence the susceptibility or resistance to PV, which needs further investigations.