{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:27Z","timestamp":1786977927495,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T00:00:00Z","timestamp":1504828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Nemours Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Esophageal pH monitoring remains a primary diagnostic tool for detecting gastroesophageal reflux disease (GERD). GERD that is refractory to proton pump inhibitor (PPI) medications may be related to\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    variants. Current PPI dosing practices in children do not take into account\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    allelic variants, which may lead to underdosing and subsequently to a misperception of PPI therapy failure. We hypothesized that pH probe acid exposure outcomes associate with\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    *\n                    <jats:italic>17<\/jats:italic>\n                    alleles among children with clinical concern for GERD. We identified a retrospective cohort of 74 children (age range 0.71\u201017.1 years, mean 8.5, SD 4.6) with stored endoscopic tissue samples and who had also undergone esophageal pH testing while on PPI therapy. These individuals were genotyped for common\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    alleles and were dichotomized to either\n                    <jats:italic>CYP2C19*17<\/jats:italic>\n                    allelic carriers without corresponding loss of function alleles as cases vs controls. Associations between pH probe acid exposure outcomes and\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    *\n                    <jats:italic>17<\/jats:italic>\n                    alleles were investigated. Compared to controls, children who carry\n                    <jats:italic>CYP2C19*17<\/jats:italic>\n                    alleles without corresponding loss\u2010of\u2010function alleles demonstrated statistically significant longer times with pH &lt; 4 (76.46 vs 33.47 minutes,\n                    <jats:italic>P<\/jats:italic>\n                    = .03); and higher percent of time with pH &lt; 4.0 (5.71 vs 2.67 minutes,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a0.04). These findings remained statistically significant using multiple\u2010regression modeling with test duration, PPI dose, and race as confounding variables. PPI therapy in children with *\n                    <jats:italic>17<\/jats:italic>\n                    alleles may be better optimized with\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotype\u2010guided dosing prior to pH probe testing.\n                  <\/jats:p>","DOI":"10.1002\/jcph.977","type":"journal-article","created":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T08:12:42Z","timestamp":1504858362000},"page":"89-96","source":"Crossref","is-referenced-by-count":26,"title":["Association Between\n                    <i>CYP2C19<\/i>\n                    *\n                    <i>17<\/i>\n                    Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal Reflux"],"prefix":"10.1002","volume":"58","author":[{"given":"James P.","family":"Franciosi","sequence":"first","affiliation":[{"name":"Division of Gastroenterology Nemours Children's Hospital Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"Mougey","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics and Translational Research Nemours Children's Health System Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Health Care Delivery Science Nemours Children's Health System Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto A.","family":"Gomez\u2010Suarez","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Nemours Children's Hospital Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Thomas","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics and Translational Research Nemours Children's Health System Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa L.","family":"Creech","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics and Translational Research Nemours Children's Health System Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"George","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics and Translational Research Nemours Children's Health System Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Corao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Alfred I. DuPont Hospital for Children Wilmington DE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Lima","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics and Translational Research Nemours Children's Health System Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3111\/13696990903378680"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181b7f563"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.14.103"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.02943.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200363240-00004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.26.386"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.11.4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000028398"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241120-00002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.20.300"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.05.037"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1151-z"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1252-3"},{"issue":"2","key":"e_1_2_9_15_1","first-page":"1","article-title":"Testing for refractory gastroesophageal reflux disease","volume":"2","author":"Zehrai A,","year":"2012","journal-title":"ASGE Leading Edge"},{"issue":"4","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.17235\/reed.2016.4232\/2016","article-title":"Proton\u2010pump inhibitors adverse effects: a review of the evidence and position statement by the Sociedad Espanola de Patologia Digestiva","volume":"108","author":"la Coba Ortiz C","year":"2016","journal-title":"Rev Esp Enferm Dig"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/gou061"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-090X(03)00103-X"},{"issue":"8","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/PAI.0b013e3182a77bfe","article-title":"Deparaffinization with mineral oil: a simple procedure for extraction of high\u2010quality DNA from archival formalin\u2010fixed paraffin\u2010embedded samples","volume":"22","author":"Heikal N","year":"2014","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mex.2014.11.003","article-title":"Improved method for extraction and detection of Helicobacter pylori DNA in formalin\u2010fixed paraffin embedded gastric biopsies using laser micro\u2010dissection","volume":"2","author":"Loayza MF","year":"2015","journal-title":"MethodsX"},{"issue":"3","key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"M179","DOI":"10.1136\/mp.49.3.M179","article-title":"A rapid and efficient method for DNA extraction from paraffin wax embedded tissue for PCR amplification","volume":"49","author":"Morgan K","year":"1996","journal-title":"Clin Mol Pathol"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.20586"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12342"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2004.04172.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.03.017"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31390"},{"issue":"3","key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.2517-6161.1988.tb01732.x","article-title":"A review of bootstrap confidence intervals","volume":"50","author":"DiCiccio TJ","year":"1988","journal-title":"J. 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