Human leukocyte antigen (HLA)-DRB1 allele polymorphisms and systemic sclerosis

Abstract

Objectives: Human leukocyteantigen (HLA) is the most important gene for immune system regulation. Although studies have evaluated the association between HLA-DRB1 allele polymorphisms and systemic sclerosis (SSc), their results are still controversial. We performed a meta-analysis to assess the association of HLA-DRB1 alleles with risk of SSc.

Methods: Electronic database were systematically searched for articles, a total of 11 case–control studies including 3268 cases and 5548 controls were analyzed. Odds ratio (ORs) and 95% confidence intervals were used to assess the association of HLA-DRB1 alleles with SSc. The relationship between SSc-related autoantibodies and DRB1 alleles was also analyzed.

Results: In the overall analysis, four alleles (DRB1*04:03, DRB1*08, DRB1*11, and DRB1*11:04) increased the risk of SSc; however, five alleles (DRB1*07, DRB1*11:01, DRB1*13, DRB1*13:01, and DRB1*14) had the opposite effect. Analysis of subgroups by ethnicity indicate that DRB1*11:01 and DRB1*13:01 confer a protective effect in Caucasians, while DRB1*11:04 was associated with a higher risk of SSc. For Asian, DRB1*13:02 was found to be a protective factor. In addition, the frequency of DRB1*11:04 alleles was significantly increased in ATA⁺ SSc patients compared with ATA⁻ SSc patients.

Conclusion: DRB1*04:03, DRB1*08, DRB1*11, and DRB1*11:04 were associated with the risk of SSc. Additionally, DRB1*11 and DRB1*11:04 were association with ATAs.

Keywords:

• SSc
• systemic sclerosis
• HLA-DRB1
• anti-topoisomerase 1 antibody
• ATA
• meta-analysis
• polymorphisms

Additional information

Funding

This work was supported by the Guangxi Nature Science Foundation (Grant number: 2016GXNSFDA380010); the Guangxi scientific research and technology development project (Grant number: Guikegong 1355005-5-7); the National Nature Science Foundation of China (Grants number: 81471498); the Shandong scientific research and technology development project (Grants number: 2014GSF118129).