The association of human leukocyte antigen class II (HLA II) haplotypes with the risk of Latent autoimmune diabetes of adults (LADA): Evidence based on available data.

Objective: Latent autoimmune diabetes in adult (LADA), classified as between type 1 and type 2 diabetes mellitus, has received widespread attention. A number of studies have investigated the association between HLA DQA-DQB, DRB-DQB haplotypes and the onset of LADA. However, the conclusions remained inconsistent. Therefore, this study aims to clarify the impact of these HLA haplotypes on the pathogenesis of LADA.

Methods: Systematic searches were carried out on the Medline, PubMed, Embase and Wan Fang respectively to investigate the association of LADA with HLA DQA-DQB, DRB-DQB up to June 05, 2020. We performed this retrospective research using meta-analysis.

Results: The pooled results demonstrated that in Chinese, DQA1*05-DQB1*0201, DQA1*03-DQB1*0401, and DQA1*03-DQB1*0303 were statistically significantly associated with increasing the risk of LADA (P < 0.001), while DQA1*0102-DQB1*0602 was statistically significantly correlated with decreasing the susceptibility to the disease (P = 0.003). However, there was no obvious association found between DQA1*0201-DQB1*0201 (P = 0.984), DQA1*03-DQB1*0302 (P = 0.110), DQA1*0601-DQB1*0301 (P = 0.398) and LADA. In Japanese, DRB1*0802-DQB1*0302 (P = 0.003) and DRB1*0901-DQB1*0303 (P = 0.001), but not DRB1*0405-DQB1*0401 (P = 0.136), were found to be a risk factor for LADA. As for Caucasian, both DRB1*03-DQB1*0201 and DRB1*04-DQB1*0302 were predisposed to the development of LADA with a statistical significance (P < 0.001).

Conclusions: In all, HLA DQA-DQB, HLA DRB-DQB haplotypes might play a role in the risk of LADA, which could provide an improved understanding of LADA pathogenesis and the detection of susceptible HLA haplotypes in the diagnosis and therapy of this disease.