{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:01:19Z","timestamp":1793260879213,"version":"4.5.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      H-type hypertension, defined as primary hypertension combined with elevated plasma homocysteine (Hcy) \u226510\u00a0\u03bcmol\/L, represents the predominant hypertensive phenotype in China. Although current guidelines recommend folic acid (FA) supplementation alongside antihypertensive therapy, a substantial treatment gap persists in routine clinical practice. The\n                      <jats:italic>MTHFR<\/jats:italic>\n                      C677T polymorphism is the principal genetic determinant of Hcy metabolism, yet its independent impact on blood pressure (BP) control in FA-untreated patients remains unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a single-centre, retrospective cohort study of 660\u00a0H-type hypertensive patients who received guideline-compliant antihypertensive therapy but no FA supplementation, enrolled from a tertiary hospital in Xinjiang, China (January 2019\u2013December 2022). The primary outcome was BP control at follow-up (systolic BP &amp;lt; 140\u00a0mmHg and diastolic BP &amp;lt; 90\u00a0mmHg). Given the known dosage effect of\n                      <jats:italic>MTHFR<\/jats:italic>\n                      C677T on enzyme activity (CC &amp;gt; CT &amp;gt; TT), we evaluated three standard genetic models: a dominant model (CC vs. CT + TT), a recessive model (CC + CT vs. TT), and an additive model (CC vs. CT vs. TT). The recessive model was used as the primary contrast in PSM analysis to evaluate the high-risk TT homozygous group while maximising matched sample size.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The overall BP control rate was 61.5% (406\/660).\n                      <jats:italic>MTHFR<\/jats:italic>\n                      genotype distribution was: CC 28.6%, CT 47.0%, TT 24.4%. In multivariable logistic regression using the recessive model, the TT genotype was associated with higher odds of uncontrolled BP compared with CC + CT carriers (OR = 1.89, 95% CI: 1.21\u20132.97; P = 0.005). LASSO-selected multivariable regression confirmed this association (OR = 1.83, 95% CI: 1.19\u20132.82; P = 0.006). After 1:2 PSM (CC + CT, n = 218; TT, n = 138), the TT genotype remained associated with higher odds of uncontrolled BP (OR = 1.75, 95% CI: 1.09\u20132.84; P = 0.022). Across all models, Grade 3 hypertension (OR range: 1.92\u20132.10 across the models), high psychological stress, high-salt dietary pattern, and physical inactivity were consistently identified as additional independent risk factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In H-type hypertensive patients not receiving FA supplementation, the\n                      <jats:italic>MTHFR<\/jats:italic>\n                      677\u00a0TT genotype was associated with poor BP control across multiple analytical models (adjusted OR range: 1.75\u20131.89 under recessive contrast; 2.06\u20132.48 under additive contrast). These findings suggest that the TT genotype may serve as a potential marker for identifying patients at higher risk of treatment resistance; whether genotype-guided FA supplementation improves BP control requires confirmation in prospective interventional studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1885629","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:25:34Z","timestamp":1788495934000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["MTHFR C677T TT genotype associated with poor blood pressure control in H-type hypertension without folic acid: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Hong","family":"Cao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Clinical Drug Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieru","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xinjiang Autonomous Region Hospital of Traditional Chinese Medicine","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Clinical Drug Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Clinical Drug Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenling","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Clinical Drug Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliye","family":"Baierdi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kashgar Prefecture Traditional Chinese Medicine Hospital","place":["Kashgar, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muyun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Clinical Drug Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Clinical Drug Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.2217\/pgs.09.61","article-title":"Pharmacogenetics of antihypertensive treatment: detailing disciplinary dissonance","volume":"10","author":"Arnett","year":"2009","journal-title":"Pharmacogenomics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD015464.pub2","article-title":"Riboflavin supplements for blood pressure lowering in adults","author":"Bradbury","year":"2025","journal-title":"Cochrane Database Syst. 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