HLA Class I Association With Autoimmune Diabetes in Chinese People: Distinct Implications in Classic Type 1 Diabetes and LADA.

CONTEXT

We aimed to investigate whether human leukocyte antigen (HLA) Class I loci differentially modulated the risk for and clinical features of Chinese people with classic type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA).

METHODS

In this case-control study, genotypes of HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 loci were obtained from 1067 cases with classic T1D, 1062 cases with LADA, and 1107 normal controls using next-generation sequencing.

RESULTS

Despite 4 alleles shared between classic T1D and LADA (protective: A02:07 and B46:01; susceptible: B54:01 and C08:01), 7 Class I alleles conferred risk exclusively for classic T1D (A24:02, B15:02, B15:18, B39:01, B40:06, B48:01, and C07:02) whereas only A02:01 was an additional risk factor for LADA. Class I alleles affected a wide spectrum of T1D clinical features, including positive rate of protein tyrosine phosphatase autoantibody and zinc transporter 8 autoantibody (A24:02), C-peptide levels (A24:02), and age at diagnosis (B46:01, C01:02, B15:02, C07:02, and C08:01). By contrast, except for the detrimental effect of C08:01 on C-peptide concentrations in LADA, no other Class I associations with clinical characteristics of LADA could be reported. The addition of Class I alleles refined the risk model consisting only of DR-DQ data in classic T1D while the overall predictive value of the LADA risk model comprising both Class I and II information was relatively low.

CONCLUSION

The attenuated HLA Class I susceptibility to LADA was indicative of a less deleterious immunogenetic nature compared with classic T1D. These autoimmune diabetes-related Class I variants might serve as additional markers in future screening among Chinese people.