{"doi":"10.2337/dc23-1947","title":"HLA Class II (<i>DR</i>, <i>DQ, DP</i>) Genes Were Separately Associated With the Progression From Seroconversion to Onset of Type 1 Diabetes Among Participants in Two Diabetes Prevention Trials (DPT-1 and TN07)","abstract":"OBJECTIVE: To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression. RESULTS: First, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression. CONCLUSIONS: These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.","journal":"Diabetes Care","year":2024,"id":438033,"datarank":0.406238309288769,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0465540183690133,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0465540183690133,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":755178,"name":"George K. Papadopoulos","orcid":"0000-0002-6944-6591","position":1,"is_corresponding":false},{"id":432889,"name":"Jay S. Skyler","orcid":"0000-0003-1136-8110","position":2,"is_corresponding":false},{"id":251269,"name":"Alberto Pugliese","orcid":"0000-0002-7211-0319","position":3,"is_corresponding":false},{"id":5962,"name":"Hemang Parikh","orcid":"0000-0002-9076-6709","position":4,"is_corresponding":false},{"id":281006,"name":"William W. Kwok","orcid":"0000-0003-4843-4599","position":5,"is_corresponding":false},{"id":435749,"name":"Terry P. Lybrand","orcid":"0000-0002-2248-104X","position":6,"is_corresponding":false},{"id":755180,"name":"George P. Bondinas","orcid":"0000-0003-0699-2664","position":7,"is_corresponding":false},{"id":755179,"name":"Antonis K. Moustakas","orcid":"0009-0003-9705-9526","position":8,"is_corresponding":false},{"id":590156,"name":"Ruihan Wang","orcid":"0000-0002-4169-4673","position":9,"is_corresponding":false},{"id":755620,"name":"Chul‐Woo Pyo","orcid":null,"position":10,"is_corresponding":false},{"id":830558,"name":"Wyatt C. Nelson","orcid":null,"position":11,"is_corresponding":false},{"id":387388,"name":"Daniel E. Geraghty","orcid":"0000-0001-7702-5650","position":12,"is_corresponding":false},{"id":95837,"name":"Åke Lernmark","orcid":"0000-0003-1735-0499","position":13,"is_corresponding":false},{"id":413884,"name":"Lue Ping Zhao","orcid":"0000-0002-1387-7165","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:00:38.888629Z","pmid":"38498185","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}