{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:18:18Z","timestamp":1785403098915,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015498","name":"Ministry for Innovation and Technology","doi-asserted-by":"publisher","award":["2020-4.1.1.-TKP2020-MOLORKIV,  2020-1.1.5-Gyorsitosav-2021-00020 P-Invent"],"award-info":[{"award-number":["2020-4.1.1.-TKP2020-MOLORKIV,  2020-1.1.5-Gyorsitosav-2021-00020 P-Invent"]}],"id":[{"id":"10.13039\/501100015498","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2020-4.1.1.-TKP2020-MOLORKIV,  2020-1.1.5-Gyorsitosav-2021-00020 P-Invent"],"award-info":[{"award-number":["2020-4.1.1.-TKP2020-MOLORKIV,  2020-1.1.5-Gyorsitosav-2021-00020 P-Invent"]}],"id":[{"id":"https:\/\/ror.org\/02ey3ab96","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020916","name":"Hungarian Research Network","doi-asserted-by":"crossref","award":["HUN-REN-SE-ENDOMOLPAT"],"award-info":[{"award-number":["HUN-REN-SE-ENDOMOLPAT"]}],"id":[{"id":"10.13039\/100020916","id-type":"DOI","asserted-by":"crossref"}]},{"award":["HUN-REN-SE-ENDOMOLPAT"],"award-info":[{"award-number":["HUN-REN-SE-ENDOMOLPAT"]}],"id":[{"id":"https:\/\/ror.org\/04w6pnc49","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hungarian Diabetes Foundation","award":["none"],"award-info":[{"award-number":["none"]}]},{"award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"https:\/\/ror.org\/03ejqwd09","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic neuropathy is a common and multifactorial complication of type 2 diabetes, in which genetic susceptibility is increasingly recognized as a contributing factor. This study (cross-sectional case\u2013control) aimed to investigate the associations between previously identified genetic variants and clinically relevant neurophysiological and symptomatic parameters. A total of 48 individuals with type 2 diabetes (24 with neuropathy and 24 without) were included. Neuropathy was assessed using standardized neurological, sensory, and cardiovascular autonomic function tests. Genetic variants were selected in a prior discovery analysis of this same cohort and re-tested here, precluding independent validation. Associations between genetic variants and clinical parameters were assessed through group-based comparisons using Mann\u2013Whitney U tests and Fisher\u2019s exact test, correlation analysis using Spearman\u2019s rank correlation, permutation-based testing to improve robustness, and multivariable linear regression adjusted for age and sex to account for potential demographic confounding (q &lt; 0.1). Mann\u2013Whitney U test analysis identified several associations between genetic variants and neuropathy-related clinical parameters. In the Mann\u2013Whitney U test analysis, only the rs6682221 variant remained significantly associated with heat detection threshold in the left hand after false discovery rate correction (p = 0.000150; q = 0.02736), although this association did not remain significant in the complementary permutation analysis based on median differences. Spearman\u2019s rank correlation analysis identified a significant positive association between rs6682221 allele burden and heat detection threshold in the left hand, which remained significant after permutation correction (r = 0.552, p = 0.000086, q = 0.016). Multivariable regression adjusted for age and sex revealed several independent associations between selected variants and sensory neuropathy-related parameters. These findings should be considered exploratory, as all analyses were performed within the original discovery cohort and no independent validation cohort was available. Independent replication and functional studies are required before any clinical relevance can be inferred.<\/jats:p>","DOI":"10.3390\/ijms27125487","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:11:22Z","timestamp":1781709082000},"page":"5487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations Between Previously Identified Genetic Variants and Clinical Phenotypes of Diabetic Neuropathy in Type 2 Diabetes: An Exploratory Analysis of the Discovery Cohort"],"prefix":"10.3390","volume":"27","author":[{"given":"No\u00e9mi","family":"Hajd\u00fa","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zs\u00f3fia","family":"Ludvig","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3na","family":"R\u00e1cz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildik\u00f3","family":"Istenes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdolna","family":"B\u00e9keffy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsolya Erzs\u00e9bet","family":"V\u00e1gi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Erzs\u00e9bet","family":"K\u00f6rei","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"T\u00f3bi\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Hungarian Research Network HUN-REN-ENDOMOLPAT, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-9015","authenticated-orcid":false,"given":"Anett","family":"Ill\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Hungarian Research Network HUN-REN-ENDOMOLPAT, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriett","family":"Pik\u00f3","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Hungarian Research Network HUN-REN-ENDOMOLPAT, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7510-8387","authenticated-orcid":false,"given":"J\u00e1nos P.","family":"K\u00f3sa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Hungarian Research Network HUN-REN-ENDOMOLPAT, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krist\u00f3f","family":"\u00c1rvai","sequence":"additional","affiliation":[{"name":"Hungarian Research Network HUN-REN-ENDOMOLPAT, 1085 Budapest, Hungary"},{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1t\u00e9","family":"Posta","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Semmelweis University, 1094 Budapest, Hungary"},{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter Andr\u00e1s","family":"Lakatos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and 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