{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T13:57:20Z","timestamp":1770731840339,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"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":["Diabet Med"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The interplay between angiogenic genetic variants and metabolic\u2010vascular comorbidities in type 2 diabetes mellitus (T2DM) remains poorly elucidated. This cohort study investigated the synergistic effects of VEGFA\u2010centric polymorphisms on hypertension (HTN) and dyslipidaemia (DYS) susceptibility in T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We enrolled 440 individuals stratified into three groups: T2DM\u2010only (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009258), T2DM+HTN (T2MH,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009130) and T2DM+HTN+DYS (T2MH\u2010DYS,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200952). Genotyping of VEGFA rs3025020, ANGPT2 rs11137037\/rs2442598, TGFB1 rs1800469 and AGTR1 rs5182 was performed using ligase\u2010mediated hybridization and multiplex PCR. Phenotypic profiling included metabolic, haemodynamic and inflammatory biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The T2MH\u2010DYS group exhibited severe metabolic dysregulation, with elevated fasting glucose (12.60\u2009\u00b1\u20097.62 vs. 7.93\u2009mmol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017), triglycerides (median 2.48 vs. 1.68\u2009mmol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and systemic inflammation (CRP: 2.65 vs. 1.79\u2009mg\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016). VEGFA rs3025020\u2010TT genotype frequency was significantly enriched in T2MH\u2010DYS (17.3% vs. 3.9% in T2DM, recessive model\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), conferring a 3.49\u2010fold comorbidity risk (95% CI: 1.10\u201311.14,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.034). ANGPT2 rs2442598\u2010CC genotype demonstrated borderline protective effects (OR\u2009=\u20090.46,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.057), while AGTR1 rs5182\u2010TT correlated with milder HTN (Grade I: 72.2% vs. Grade III: 46.6%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008). Haplotype analysis revealed synergistic risks: C\u2010C\u2010T (AGTR1\u2010ANGPT2\u2010VEGFA) increased T2MH\u2010DYS susceptibility 3.58\u2010fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0019), whereas C\u2010T\u2010C exhibited protection (OR\u2009=\u20090.333,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.013).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings underscored VEGFA rs3025020 as a genetic hub coordinating multilocus angiogenic dysregulation, driving HTN and DYS pathogenesis in T2DM. Our results highlight the potential for genotype\u2010guided anti\u2010angiogenic therapies to mitigate metabolic\u2013vascular deterioration in high\u2010risk diabetic populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.70169","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T04:05:06Z","timestamp":1763006706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>VEGFA<\/scp>\n                    \u2010centric angiogenic genetic variants drive hypertension and dyslipidaemia susceptibility in type 2 diabetes mellitus: A multilocus synergistic cohort study"],"prefix":"10.1111","volume":"43","author":[{"given":"Chao","family":"Zuo","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory The First Affiliated Hospital of Guilin Medical University  Guilin Guangxi 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