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

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. 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. 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). 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.