{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:35:25Z","timestamp":1774596925758,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The programmed cell death 1 (PD-1)\/PD-L1 pathway plays a critical role in immune tolerance and has been implicated in type 1 diabetes mellitus (T1DM). However, the associations between PD-1 polymorphisms, circulating soluble PD-1 (sPD-1), and T1DM susceptibility remain unclear in Chinese populations. This study evaluated the relationships of PD-1 rs2227981 and rs2227982 variants and serum sPD-1 levels with T1DM risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>89 T1DM patients and 70 healthy controls were enrolled. Genotyping was performed using TaqMan assays. Serum sPD-1 levels were measured by enzyme linked immunosorbent assay (ELISA) in a subset (44 T1DM, 28 controls). Genetic associations were assessed using multivariable logistic regression adjusting for sex, age, uric acid (UA), and triglycerides (TG).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant differences in allele and genotype distributions of rs2227981 and rs2227982 were observed between groups. After adjustment, rs2227981 was significantly associated with T1DM under recessive (adjusted OR\u00a0=\u00a00.160,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.027) and codominant models (adjusted OR\u00a0=\u00a06.764,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.024). Rs2227982 remained significantly associated under additive (adjusted OR\u00a0=\u00a01.770,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.012), dominant (adjusted OR\u00a0=\u00a00.454,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.039), recessive (adjusted OR\u00a0=\u00a00.449,\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.032), and codominant models (adjusted OR\u00a0=\u00a00.319,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.012). In genotype\u2013phenotype analysis, rs2227982 was associated with HbA1c levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.036). Serum sPD-1 concentrations were elevated in T1DM patients (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.013) but showed no correlation with glycemic parameters, autoantibody status, or PD-1 genotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PD-1 rs2227981 and rs2227982 polymorphisms are associated with T1DM susceptibility in a Chinese Han cohort. Rs2227982 may be linked to glycemic phenotype, while elevated sPD-1 levels suggest altered immune checkpoint regulation rather than reflecting short-term metabolic control. Larger and longitudinal studies are needed to confirm these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1783770","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:38:03Z","timestamp":1774593483000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of PD-1 gene polymorphisms and serum soluble PD-1 levels with type 1 diabetes mellitus susceptibility in a Chinese Han cohort: a case-control study"],"prefix":"10.3389","volume":"17","author":[{"given":"Renhao","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University","place":["Lianyungang, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuli","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University","place":["Lianyungang, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University","place":["Lianyungang, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University","place":["Lianyungang, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Management of Hospital Infection, The Affiliated Lianyungang Hospital of XuZhou Medical University, The Affiliated Hospital of Kangda College of Nanjing Medical University","place":["Lianyungang, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guofeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University","place":["Lianyungang, Jiangsu, China"]},{"name":"Department of Endocrinology, The Affiliated Lianyungang Hospital of XuZhou Medical University, The Affiliated Hospital of Kangda College of Nanjing Medical University","place":["Lianyungang, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S0140-6736(18)30024-2","article-title":"Type 1 diabetes","volume":"391","author":"Barnett","year":"2018","journal-title":"Lancet (Lond Engl)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2196\/59579","article-title":"Effectiveness of telemedicine-delivered carbohydrate-counting interventions in patients with type 1 diabetes: systematic review and meta-analysis","volume":"27","author":"Li","year":"2025","journal-title":"J Med Internet Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/dci21-0043","article-title":"The management of type 1 diabetes in adults. 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