HLA genetic discrepancy between latent autoimmune diabetes in adults and type 1 diabetes: LADA China Study 6.

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HLA genetic discrepancy between latent autoimmune diabetes in adults and type 1 diabetes: LADA China Study 6.

J Clin Endocrinol Metab. 2016 Feb 11;:jc20153771

Authors: Luo S, Lin J, Xie Z, Xiang Y, Zheng P, Huang G, Li X, Liao Y, Hagopian WA, Wang CY, Zhou Z

Abstract
CONTEXT: The discrepancies in terms of HLA-DRB1-DQA1-DQB1 conferred risks between latent autoimmune diabetes in adults (LADA) and type 1 diabetes (T1D) patients remained almost completely unknown. The goal of current study is to determine and compare HLA conferred risks between LADA and T1D.
DESIGN: A case-control study was conducted in a representative Chinese dataset containing 520 T1D patients, 562 LADA patients, and 1065 controls. The frequencies and odds ratios for HLA susceptible haplotypes and genotypes, and for arginine at residue 52 (Arg52) in DQ alpha chain or aspartic acid at residue 57 (Asp57) in DQ beta chain, were analyzed.
RESULTS: DRB1*0405-DQA1*03-DQB1*0401 and DRB1*0901-DQA1*03- DQB1*0303 are the major LADA susceptible haplotypes, which also confer comparable risks for T1D (OR: 2.02 vs. 2.20; 1.61 vs. 2.30, respectively). The strongly-associated T1D haplotype DRB1*0301-DQA1*05-DQB1*0201 is also associated with LADA, but only confer half of the T1D risk (OR: 2.65 vs. 4.84). Interestingly, the most susceptible T1D haplotypes DRB1*0901-DQA1*05-DQB1*0201, DRB1*0301-DQA1*03-DQB1*0201 and DRB1*0301-DQA1*03-DQB1*0303 are not associated with LADA. Genotypes for DR3/DR3, DR3/DR9 and DR9/DR9 are highly associated with T1D susceptibility, while only DR9/DR9 confers risk for LADA. DR3/DR3 is the high-risk genotype in Chinese T1D patients, which manifests similar risk as the DR3/DR4 genotype in Caucasians but with a lower frequency. DR9/DR9 is the high risk LADA genotype in Chinese. Alleles with DQ alpha Arg52-positive, DQ beta Asp57-negative and their combination formed in cis or trans confer susceptibility to T1D but not to LADA.
CONCLUSION: Our results suggest that LADA risk conferred by HLA-DRB1-DQA1-DQB1 loci in Chinese differs significantly from that of T1D risk. This information would be useful for classifying Asian LADA patients, which should provides novel insight into the understanding of its pathoetiology as well.

PMID: 26866570 [PubMed - as supplied by publisher]

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