Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis
Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their associat...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/7/3685 |
| _version_ | 1797212478270078976 |
|---|---|
| author | Paula Soria-Chacartegui Marcos Navares-Gómez Francisca Molina-Jiménez Emilio J. Laserna-Mendieta Laura Arias-González Pedro Majano Sergio Casabona Alfredo J. Lucendo Francisco Abad-Santos Cecilio Santander Pablo Zubiaur |
| author_facet | Paula Soria-Chacartegui Marcos Navares-Gómez Francisca Molina-Jiménez Emilio J. Laserna-Mendieta Laura Arias-González Pedro Majano Sergio Casabona Alfredo J. Lucendo Francisco Abad-Santos Cecilio Santander Pablo Zubiaur |
| author_sort | Paula Soria-Chacartegui |
| collection | DOAJ |
| description | Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (<i>STAT6</i>), <i>CYP2C19</i>, <i>CYP3A4</i>, <i>CYP3A5,</i> and <i>ABCB1</i> genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, <i>p</i> = 0.003). <i>STAT6</i> rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, <i>p</i> = 0.027). EREFS reduction in <i>STAT6</i> rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. −75.0% <i>p</i> = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in <i>STAT6</i> rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, <i>p</i> = 0.030). <i>STAT6</i> rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants. |
| first_indexed | 2024-04-24T10:43:01Z |
| format | Article |
| id | doaj.art-2935dca5eebe426d97994ce8957bb435 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:43:01Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2935dca5eebe426d97994ce8957bb4352024-04-12T13:19:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01257368510.3390/ijms25073685Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic EsophagitisPaula Soria-Chacartegui0Marcos Navares-Gómez1Francisca Molina-Jiménez2Emilio J. Laserna-Mendieta3Laura Arias-González4Pedro Majano5Sergio Casabona6Alfredo J. Lucendo7Francisco Abad-Santos8Cecilio Santander9Pablo Zubiaur10Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainInstituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, SpainInstituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, SpainInstituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, SpainInstituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, SpainInstituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, SpainInstituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainInstituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainProton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (<i>STAT6</i>), <i>CYP2C19</i>, <i>CYP3A4</i>, <i>CYP3A5,</i> and <i>ABCB1</i> genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, <i>p</i> = 0.003). <i>STAT6</i> rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, <i>p</i> = 0.027). EREFS reduction in <i>STAT6</i> rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. −75.0% <i>p</i> = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in <i>STAT6</i> rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, <i>p</i> = 0.030). <i>STAT6</i> rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.https://www.mdpi.com/1422-0067/25/7/3685<i>STAT6</i>pharmacogeneticseosinophilic esophagitis<i>CYP2C19</i> |
| spellingShingle | Paula Soria-Chacartegui Marcos Navares-Gómez Francisca Molina-Jiménez Emilio J. Laserna-Mendieta Laura Arias-González Pedro Majano Sergio Casabona Alfredo J. Lucendo Francisco Abad-Santos Cecilio Santander Pablo Zubiaur Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis International Journal of Molecular Sciences <i>STAT6</i> pharmacogenetics eosinophilic esophagitis <i>CYP2C19</i> |
| title | Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis |
| title_full | Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis |
| title_fullStr | Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis |
| title_full_unstemmed | Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis |
| title_short | Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis |
| title_sort | impact of i stat6 i variants on the response to proton pump inhibitors and comorbidities in patients with eosinophilic esophagitis |
| topic | <i>STAT6</i> pharmacogenetics eosinophilic esophagitis <i>CYP2C19</i> |
| url | https://www.mdpi.com/1422-0067/25/7/3685 |
| work_keys_str_mv | AT paulasoriachacartegui impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT marcosnavaresgomez impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT franciscamolinajimenez impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT emiliojlasernamendieta impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT lauraariasgonzalez impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT pedromajano impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT sergiocasabona impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT alfredojlucendo impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT franciscoabadsantos impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT ceciliosantander impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis AT pablozubiaur impactofistat6ivariantsontheresponsetoprotonpumpinhibitorsandcomorbiditiesinpatientswitheosinophilicesophagitis |