{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:10:26Z","timestamp":1783923026552,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010724","name":"Health Systems Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010724","id-type":"DOI","asserted-by":"publisher"}]}],"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>Phenytoin is an anticonvulsant used to treat epilepsy and prevent perioperative seizures. However, genetic prediction of phenytoin-induced cutaneous adverse reactions (PHT-cADRs) and the co-contributing role of non-genetic factors remain unclear. We aimed to evaluate genetic and non-genetic factors associated with PHT-cADRs in a Southern Thai population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A case\u2013control study was conducted involving 104 patients (26 with PHT-cADRs confirmed by a dermatologist or allergist and 78 phenytoin-tolerant controls). Patient history (demographics, comorbidities, and co-medications) and laboratory parameters (complete blood count and clinical chemistry indicators) during phenytoin initiation were reviewed. Genetic markers including\n                      <jats:italic>CYP2C9<\/jats:italic>\n                      ,\n                      <jats:italic>HLA-A<\/jats:italic>\n                      ,\n                      <jats:italic>HLA-B<\/jats:italic>\n                      , and\n                      <jats:italic>HLA-DRB1<\/jats:italic>\n                      were studied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A significant difference in sex was observed among the patients (73.1% female patients in the PHT-cADR group vs. 44.9% in the control group; P = 0.014). Baseline clinical indications differed marginally between the groups; the case group had more neurosurgical patients and fewer patients with epilepsy than the control group. Other non-genetic factors were not significantly associated with PHT-cADRs. For laboratory data, the case group showed significantly lower mean hemoglobin (11.73\u00a0g\/dL vs. 13.48\u00a0g\/dL, P = 0.0005) and hematocrit levels (35.94% vs. 40.29%, P = 0.0019) and a higher mean white blood cell count (10.19 \u00d7 10\n                      <jats:sup>3<\/jats:sup>\n                      \/\u03bcL vs. 7.75 \u00d7 10\n                      <jats:sup>3<\/jats:sup>\n                      \/\u03bcL, P = 0.0083) than the control group. For genetic factors, decreased CYP2C9 function [odds ratio (OR) = 7.89; 95% confidence interval (CI) = 1.81\u201334.49; P = 0.006] and\n                      <jats:italic>HLA-B*40:06<\/jats:italic>\n                      (OR = 6.26; 95% CI = 1.59\u201324.69; P = 0.009) were associated with an increased risk of PHT-cADRs. No HLA marker reached a significant level after Bonferroni correction. Multivariate analysis was not performed owing to a high proportion of missing laboratory data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>HLA-B<\/jats:italic>\n                      alleles and CYP2C9 function were associated with PHT-cADRs. As an exploratory observation, our findings suggest that lower hemoglobin levels and higher white blood cell counts are associated with PHT-cADRs. However, the limited sample size, particularly in the case group, may have led to false-positive and -negative results. Therefore, these findings should be interpreted with caution, and a larger study is required to confirm the contribution of these hematological factors.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1827880","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:34:06Z","timestamp":1783920846000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of decreased CYP2C9 function, HLA-B*40:06, and hemoglobin levels with phenytoin-induced cutaneous adverse reactions in a Southern Thai population"],"prefix":"10.3389","volume":"17","author":[{"given":"Chutima","family":"Seree-aphinan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai\/Songkhla, 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