Ying Xia1, Xia Li1, Gan Huang1, Jian Lin1, Shuoming Luo1, Zhiguo Xie2, Zhiguang Zhou3. 1. 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. 2. 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. Electronic address: xiezhiguo@csu.edu.cn. 3. 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. Electronic address: zhouzhiguang@csu.edu.cn.
Abstract
AIMS: 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. METHODS: 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. RESULTS: In the direct comparison, DPA1*01:03, DPB1*04:01 and DPA1*01:03-DPB1*04:01 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 DPA1*02:02-DPB1*02:02 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. CONCLUSION: 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.
AIMS: 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. METHODS: 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. RESULTS: In the direct comparison, DPA1*01:03, DPB1*04:01 and DPA1*01:03-DPB1*04:01 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 DPA1*02:02-DPB1*02:02 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. CONCLUSION: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.