{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:37:10Z","timestamp":1773794230739,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":331,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012173","name":"China-Japan Friendship Hospital","doi-asserted-by":"publisher","award":["ZRJY2024-GG07"],"award-info":[{"award-number":["ZRJY2024-GG07"]}],"id":[{"id":"10.13039\/501100012173","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012173","name":"China-Japan Friendship Hospital","doi-asserted-by":"publisher","award":["ZRJY2024-BJ02"],"award-info":[{"award-number":["ZRJY2024-BJ02"]}],"id":[{"id":"10.13039\/501100012173","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104601"],"award-info":[{"award-number":["82104601"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474247"],"award-info":[{"award-number":["82474247"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Diabetic kidney disease (DKD) is a leading cause of end\u2010stage renal disease (ESRD). The dysregulation of lipoic acid synthase (\n                      <jats:italic>LIAS<\/jats:italic>\n                      ) gene, which plays an essential role in the maintenance of mitochondrial function, was reported to participate in DKD pathogenesis. Therefore, the present study aimed to explore the association of\n                      <jats:italic>LIAS<\/jats:italic>\n                      gene methylation with the risk for DKD. DNA methylation has emerged as a potential biomarker for DKD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cohort of 308 patients, comprising 156 patients with Type 2 diabetes mellitus (T2DM) with DKD (DKD group) and 152 with T2DM alone (T2DM group), were involved in the present study. A methylation\u2010sensitive restriction endonuclease (MSRE)\u2010qPCR approach combined with three enzymes (HpaII, AciI, and Hin6I) was developed to examine methylation patterns of the promoter region and exon 1 of\n                      <jats:italic>LIAS<\/jats:italic>\n                      gene. Logistic regression analysis was performed to evaluate the associations between methylation levels and DKD risk, and then the clinical conventional confounders, including age, sex, BMI, hypertension, and lipid profiles, were adjusted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We successfully identified the methylation sites that can be recognized and digested by HpaII, AciI, and Hin6I, in the CpG islands of\n                      <jats:italic>LIAS<\/jats:italic>\n                      promoter region and exon 1. Applying the MSRE\u2010qPCR approach, significant differences in methylation levels were observed at two CpG sites. Compared with T2DM group, the P3 site in the promoter region exhibited increased methylation level in the DKD group (5.886% vs. 10.229%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.043), whereas E1 site in exon 1 showed reduced methylation level in the DKD group (11.785% vs. 6.250%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.023). Furthermore, logistic regression revealed that increased methylation at P3 was associated with increased DKD risk [OR (95% CI) 1.029 (1.011, 1.047),\n                      <jats:italic>p<\/jats:italic>\n                      = 0.002], whereas increased methylation at E1 demonstrated a protective effect [OR (95% CI) 0.940 (0.896, 0.987),\n                      <jats:italic>p<\/jats:italic>\n                      = 0.013]. Then, via including P3 and E1 sites in the same model, we found both sites independently influenced the risk for DKD. In addition, these associations were not significantly altered after adjusted for the confounders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The findings indicate that\n                      <jats:italic>LIAS<\/jats:italic>\n                      gene methylation participate in DKD pathogenesis, providing novel insights into its pathophysiological mechanisms. It highlighted that\n                      <jats:italic>LIAS<\/jats:italic>\n                      methylation could serve as a promising biomarker for DKD. Also, it supported the utility of MSRE\u2010qPCR in clinical applications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jdr\/4342250","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T15:06:28Z","timestamp":1764342388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Association of Lipoic Acid Synthase (\n                    <i>LIAS<\/i>\n                    ) Gene Methylation With Diabetic Kidney 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