The Role of HLA Class II Two‐Locus Haplotypes and Genotypes in Chinese With Type 1 Diabetes

AIMS: The role of two-locus haplotypes and genotypes of human leucocyte antigen (HLA) class II genes in Chinese type 1 diabetes (T1D) remains unclear. We investigated the susceptibility associated with HLA DR-DQ haplotypes and genotypes in Chinese patients, compared it with that in Caucasians, and analysed the rate of islet autoantibody positivity in T1D patients carrying different susceptible haplotypes. MATERIALS AND METHODS: In this case-control study, peripheral blood samples were collected from 626 T1D patients and 1065 healthy controls. HLA-DR-DQ genotyping was performed using polymerase chain reaction sequencing-based methods. Islet autoantibodies were identified using radioligand assays. RESULTS: ). The first two genotypes are also susceptible to Caucasian T1D populations but exhibit significantly different frequencies and relative risks. The third genotype is specific to Chinese T1D patients. Additionally, four haplotypes DQA1*03-DQB1*04:01, DQA1*03-DQB1*03:03, DRB1*03:01-DQA1*03, and DRB1*03:01-DQB1*03:03 were identified as susceptibility haplotypes specific to Chinese T1D patients. Haplotypes and genotypes involving the DRB1*09:01 allele are commonly observed in East Asian populations. However, these haplotypes are not associated with disease susceptibility in Caucasian populations. Moreover, patients carrying the susceptible DQA1*03-DQB1*03:03, DRB1*09:01-DQA1*03, or DRB1*09:01-DQB1*03:03 haplotypes exhibited a higher IA-2A positivity rate than those carrying the non-carrier haplotypes. Conversely, individuals with the DRB1*09:01-DQA1*03 haplotype showed a significantly lower ZnT8A positivity rate compared with non-carriers (p = 0.0312). CONCLUSIONS: This study demonstrates significant differences in the HLA-DR-DQ haplotypes and genotypes associated with T1D susceptibility between Chinese and Caucasian populations. Specific haplotypes, particularly those involving the DRB1*09:01 allele, are unique to the East Asian patients and exhibit distinct islet autoantibody profiles. These findings emphasise the importance of considering ethnic-specific genetic markers in the study and management of T1D.