National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
Diabetes Res Clin Pract. 2021 Mar;173:108582. doi: 10.1016/j.diabres.2020.108582. Epub 2020 Dec 8.
To determine if HLA-DP loci independently contribute to classic type 1 diabetes (T1D) of all ages, childhood-onset T1D and latent autoimmune diabetes in adults (LADA) among Chinese Han population.
A total of 518 patients with classic T1D (Among them 180 participants manifested T1D between 1 and 14 years), 519 patients with LADA and 527 normal controls were genotyped for both HLA-DPA1 and -DPB1 loci. The frequencies of DP alleles and haplotypes in patients were directly compared to those in controls, followed by adjustment for linkage disequilibrium (LD) with DR-DQ haplotypes.
In the direct comparison, DPA101:03, DPB104:01 and DPA101:03-DPB104:01 showed disease-predisposing effects in both the overall T1D group and the childhood-onset T1D group mainly due to their conjunction with the known susceptible DR3 haplotype. Conditioning on DR-DQ haplotypes, only DPA102:02-DPB102:02 significantly increased T1D risk among those diagnosed during childhood (OR = 2.02, 95% CI = 1.35-3.01). Whether or not adjusted for LD, no statistically significant HLA-DP association could be observed for LADA.
HLA-DP is implicated in the pathogenesis of childhood-onset T1D in Chinese, independent of the predominant DR-DQ loci and might serve as additional markers in genetic models for the recognition of those genetically at-risk individuals.
确定 HLA-DP 基因座是否独立于中国汉族人群的所有年龄段、儿童起病的 1 型糖尿病（T1D）和成人隐匿性自身免疫性糖尿病（LADA）之外，对经典 1 型糖尿病（T1D）有影响。
对 518 例经典 T1D 患者（其中 180 例患者在 1 至 14 岁之间发病）、519 例 LADA 患者和 527 例正常对照者进行 HLA-DPA1 和-DPB1 基因座的基因分型。将患者的 DP 等位基因和单体型频率与对照组进行直接比较，然后对 DR-DQ 单体型的连锁不平衡（LD）进行调整。
在直接比较中，DPA101:03、DPB104:01 和 DPA101:03-DPB104:01 在整体 T1D 组和儿童起病 T1D 组中均表现出疾病易感性，这主要是由于它们与已知的易感 DR3 单体型相结合。在考虑 DR-DQ 单体型的情况下，只有 DPA102:02-DPB102:02 在儿童期诊断的患者中显著增加 T1D 风险（OR=2.02，95%CI=1.35-3.01）。无论是否调整 LD，在 LADA 中均未观察到 HLA-DP 的统计学显著关联。
HLA-DP 参与了中国儿童起病的 T1D 的发病机制，独立于主要的 DR-DQ 基因座，并且可能作为遗传模型中识别那些遗传易感个体的附加标记。
