{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T07:17:33Z","timestamp":1784791053584,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":202,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Nutrition and Metabolism"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      This cross\u2010sectional case\u2013control study aimed to investigate the association between germline and sporadic variations in the\n                      <jats:italic>Insulin Receptor (INSR)<\/jats:italic>\n                      gene, risk factors, and the differential expression of circulating miRNA\u201021 and miRNA\u2010146a in the onset of Type 2 diabetes mellitus (T2DM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      A total of 800 T2DM patients and 600 nondiabetic age\u2010 and gender\u2010matched individuals participated in single nucleotide polymorphism (SNPs) screening in the\n                      <jats:italic>INSR<\/jats:italic>\n                      gene via polymerase chain reaction (PCR), followed by Sanger sequencing. Transcriptional expression was quantified using reverse transcriptase PCR (RT\u2010PCR). Relative expression levels of circulating miRNAs were determined by real\u2010time PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) association of Exon 17\n                      <jats:italic>INSR<\/jats:italic>\n                      SNPs with T2DM, including a single base substitution mutation at Codon 115 (rs1799817; CAC\u2009&gt;\u2009CAT) and Codon 83 (rs1799816; GGT\u2009&gt;\u2009GAT), was found. However, a deletion mutation at Codon 186 (rs1052371; delT) showed no significant association with the disease. Linkage disequilibrium analysis (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009&gt;\u20090.8) indicated a strong correlation among these SNPs and T2DM.\n                      <jats:italic>INSR<\/jats:italic>\n                      and miRNA\u201021 levels were significantly downregulated in T2DM patients, while circulating miRNA\u2010146a was upregulated, as shown by relative expression analysis. ROC curve analysis indicated that miRNA\u201021 and miRNA\u2010146a exhibited high diagnostic efficacy for T2DM. Furthermore, combined detection of these miRNAs showed greater potential as biomarkers for insulin resistance and metabolic complications in T2DM, particularly in this study population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study highlights a significant association between SNPs in Exon 17 of\n                      <jats:italic>INSR<\/jats:italic>\n                      and the differential expression of circulating miRNAs in T2DM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jnme\/9980111","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:50:55Z","timestamp":1784789455000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic and Transcriptomic Variations of\n                    <i>INSR<\/i>\n                    Are Associated With Dysregulation of Circulatory miRNA\u201021 and miRNA\u2010146a in Type 2 Diabetes Mellitus"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9661-5898","authenticated-orcid":false,"given":"Hira","family":"Gul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-6587","authenticated-orcid":false,"given":"Nosheen","family":"Masood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2007.10.019"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.2007.s36"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes10120984"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.225"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)92694-o"},{"key":"e_1_2_9_6_2","volume-title":"Endotext","author":"De Meyts P.","year":"2000"},{"key":"e_1_2_9_7_2","first-page":"418","article-title":"Polymorphisms of Exon 17 of Insulin-Receptor Gene in Pathogenesis of Human Disorders With Insulin Resistance","volume":"17","author":"Wang L. 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