Association between HLA class I genes and onset ages of type 1 diabetes (T1D) has been reported in Europeans—risk A*2402 and B*3906 were associated with an earlier age at onset. However, there exists considerable heterogeneity in different populations and individuals of T1D. Its incidence varies dramatically by country and region, ranging from > 60 per 100000 persons years in Finland to 1.01 per 100000 persons years in China. With latter, as many as 65% of the newly diagnosed patients occurred among adults. Furthermore, little is known about the distribution of HLA class I alleles in Chinese patients with T1D at different onset ages. To clarify the contribution of HLA class I genes to T1D with different onset ages in Chinese, 376 patients with T1D and 500 healthy controls were enrolled in this study to analyze HLA-A, B, C alleles conditioning on DRB1-DQA1-DQB1 haplotypes. Among them, 159 patients with an onset age < 15 years were assigned into early-onset group (EG) while the rest 217 patients constituted the late-onset group (LG). After adjustment for linkage disequilibrium with HLA class II, A*24:02:01 (OR 2.7), B*54:01:01 (OR 4.1)and C*15:02:01 (OR 7.8) were associated with susceptibility in EG patients, while A*24:02:01 (OR 2.3), B*15:02:01 (OR 2.5), B*54:01:01 (OR 3.6)and C*08:01:01 (OR 2.0)were predisposing in LG patients when compared with control subjects. Besides, B*46:01:01 (OR 0.4)conferred protection against T1D in EG patients, while B*46:01:01 (OR 0.5)and A*02:07:01 (OR 0.6)were protective in LG patients. When comparing the distribution of HLA class I genes between EG and LG, the data showed that the frequency of A*11:01:01 was higher in LG than EG. When A*11:01:01 was analyzed in patients at all ages using linear regression, it showed a positive correlation between A*11:01:01 and T1D onset age.
In conclusion, the data showed that HLA class I alleles play a role in susceptibility to T1D with different onset ages among Chinese patients, which is independent from DR-DQ haplotypes.
Z. Jiang: None. W. Ren: None. Y. Xian: None. J. Yan: None. D. Yang: None. S. Luo: None. X. Zheng: None. W. Xu: None. J. Bei: None. L. Groop: None. J. Weng: None.
National Natural Science Foundation of China (81530025); National Key Research and Development Program of China (2017YFC1309603); Sun Yat-sen University (2007030)