Association of HLA class I and class II alleles with bullous pemphigoid in Chinese Hans

Abstract

Background: Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases. Associations of genes, especially human leukocyte antigen (HLA)-DQ alleles, with BP indicate that genetic predisposition contributes to the disease.

Objectives: To evaluate the association of HLA class I and HLA class II alleles with susceptibility to BP in the northern Chinese Han population.

Methods: We performed genotype for HLA-A, -B, -C, -G, -DPA1, -DPB1, -DQA1, -DQB1 and -DRB1 loci in 105 patients with BP by Sanger sequence-based typing (SBT) method. These data were compared with a local control cohort of 420 age- and sex-matched cases.

Results: Among the HLA alleles described herein, the susceptibility alleles associated with a high prevalence of BP were A*11:01 (OR = 1.9 Pc = 0.017); B*37:01 (OR = 8, Pc = 1.811 × 10^-6); G*01:01 (OR = 3.61, Pc = 2.839 × 10^-15) and G*01:06 (OR = 2.22, Pc = 0.025); DQA1*01:05 (OR = 4.87, Pc = 5.822 × 10^-5), DQA1*05:05 (OR = 2.64, Pc = 9.114 × 10^-4), and DQA1*05:08 (OR = 10.2, Pc = 0.016); DQB1*03:01 (OR = 1.69, Pc = 0.048) and DQB1*05:01 (OR = 3.42, Pc = 7.28 × 10^-6); and DRB1*10:01 (OR = 6.85, Pc = 2.63 × 10^-6). To the contrary, HLA-DQA1*01:02 (OR = 0.46, Pc = 8.603 × 10^-4) and DQA1*01:03 (OR = 0.38, Pc = 0.048); DQB1*02:02 (OR = 0.28, Pc = 0.016); and DRB1*07:01 (OR = 0.26, Pc = 0.004) had significant associations with protection against BP. In addition, the frequency of haplotype HLA-DRB1*13-DQA1*05-DQB1*03 (OR = 12.32, Pc = 0.026) in BP patients was significantly higher than those in controls.

Conclusion: Our data demonstrated that the alleles and haplotypes found in this study may be important differential genetic markers for susceptibility to or protection against BP in individuals of northern Chinese Han population.

Keywords: Bullous pemphigoid; HLA class I; HLA class II; Haplotypes.