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.