Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis
Abstract
:1. Introduction
2. Results
2.1. Baseline Characteristics
2.2. Impact of STAT6 Genetic Variation in Baseline Scores
2.3. Impact of STAT6 Genetic Variation on Symptom Onset and Comorbidity
2.4. Treatment Effectiveness
2.5. Correlation between Severity Scores
2.6. Impact of Genetic Variation on Effectiveness Variables and Histological Response
2.7. Impact of Genetic Variation on Symptom Variations
3. Discussion
4. Materials and Methods
4.1. Study Population and Procedures
4.2. Esophageal Biopsies Processing, Genotyping, and Phenotyping
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Demographic Characteristics | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Variable | n | Age (Years) | Height (m) | Weight (kg) | BMI (kg/m2) | |||||
Mean | SD | Mean | SD | Mean | SD | Mean | SD | |||
Sex | Men | 25 | 42.24 | 13.33 | 1.79 | 0.09 | 81.94 | 13.00 | 25.62 | 3.15 |
Women | 3 | 31.67 | 31.67 | 1.66 * | 0.03 | 59.33 * | 9.29 | 21.55 * | 2.56 | |
Total | 28 | 41.11 | 13.13 | 1.77 | 0.09 | 79.52 | 14.40 | 25.18 | 3.31 | |
Clinical characteristics | ||||||||||
Symptom incidence | Dysphagia | 27 out of 28 (96.43%) | Regurgitation | 6 out of 28 (21.43%) | ||||||
Food impaction | 22 out of 28 (78.57%) | Chest pain | 5 out of 28 (17.86%) | |||||||
Heartburn | 8 out of 28 (28.57%) | Abdominal pain | 2 out of 28 (7.14%) | |||||||
Vomiting | 6 out of 28 (21.43%) | Nausea | 2 out of 28 (7.14%) | |||||||
Atopic disease incidence | Allergic rhinoconjunctivitis | 23 out of 28 (82.1%) | Food allergy | 8 out of 28 (28.57%) | ||||||
Asthma | 9 out of 28 (32.14%) | Eczema | 3 out of 28 (10.7%) |
Variable | N | Baseline PEC (Cells/Hpf) | Baseline EREFS (Score) | Disease Duration (Years) | ||||
---|---|---|---|---|---|---|---|---|
Mean | SD | Mean | SD | Median | IQR | |||
Sex | Men | 25 | 68.56 | 45.39 | 4.32 | 1.95 | 3.00 | 0.00–10.50 |
Women | 3 | 55.00 | 30.41 | 3.33 | 1.15 | 1.00 | - | |
Treatment | Omeprazole | 15 | 59.67 | 51.74 | 3.73 | 2.09 | 1.00 | 0.00–10.00 |
Esomeprazole | 4 | 72.50 | 17.08 | 4.75 | 1.71 | 9.50 | 6.75–32.50 | |
Pantoprazole | 5 | 62.00 | 26.83 | 4.00 | 1.41 | 3.00 | 1.50–17.50 | |
Lansoprazole | 4 | 96.00 | 45.28 | 5.75 | 1.26 | 3.00 | 0.00–21.00 | |
STAT6 g.18453G>C (rs12368672) | G/G | 13 | 83.23 * | 50.86 | 4.62 | 1.50 | 3.00 | 0.00–18.00 |
G/C | 13 | 55.15 | 34.22 | 4.15 | 2.19 | 2.00 | 0.50–9.50 | |
C/C | 2 | 40.00 | 0.00 | 2.00 | 0.00 | 10.50 | - | |
STAT6 g.27148G>A (rs167769) | G/G | 11 | 66.46 | 28.20 | 4.18 | 1.25 | 2.00 | 0.00–10.00 |
G/A | 17 | 67.53 | 52.34 | 4.24 | 2.25 | 3.00 | 0.00–10.50 | |
STAT6 g.28741G>A (rs324011) | G/G | 10 | 69.80 | 27.33 | 4.10 | 1.29 | 2.00 | 0.00–14.75 |
G/A + A/A | 18 | 65.61 | 51.43 | 4.28 | 2.19 | 4.50 | 0.50–10.50 | |
STAT6 g.37927C>T (rs841718) | C/C | 3 | 62.67 | 21.94 | 3.33 | 0.58 | 2.00 | - |
C/T | 17 | 59.24 | 33.40 | 4.18 | 1.78 | 2.00 | 0.00–9.00 | |
T/T | 8 | 85.50 | 64.55 | 4.63 | 2.45 | 6.00 | 0.50–13.75 | |
STAT6 g.38178C>T (rs3024974) | C/C | 19 | 68.53 | 49.54 | 4.11 | 2.03 | 6.00 | 1.00–10.00 |
C/T | 9 | 64.11 | 30.60 | 4.44 | 1.67 | 1.00 | 0.00–20.00 | |
STAT6 g.40823A>G (rs324015) | A/G | 9 | 61.67 | 35.00 | 3.78 | 1.20 | 6.00 | 2.00–15.00 |
G/G | 19 | 69.68 | 48.08 | 4.42 | 2.14 | 1.00 | 0.00–10.00 | |
STAT6 g.41214A>G (rs1059513) | A/A | 21 | 63.38 | 47.22 | 3.95 | 1.96 | 2.00 | 0.00–10.00 |
A/G | 7 | 78.29 | 31.74 | 5.00 | 1.53 | 9.00 | 0.00–15.00 | |
TOTAL | 28 | 67.11 | 43.80 | 4.21 | 1.89 | 2.50 | 0.00–10.00 |
STAT6 Variant | Genotype | Symptom/Comorbidity | Patients Affected | Significance |
---|---|---|---|---|
g.27148G>A (rs167769) | G/G | Heartburn | 6 of 11 (54.55%) | p = 0.030 |
G/A | 2 of 17 (11.77%) | |||
g.18453G>C (rs12368672) | G/G | 6 of 13 (46.15%) | p = 0.096 | |
G/C | 1 of 13 (7.69%) | |||
C/C | 1 of 2 (50%) | |||
g.28741G>A (rs324011) | G/G | 5 of 10 (50%) | p = 0.091 | |
G/A + A/A | 3 of 18 (16.67%) | |||
g.18453G>C (rs12368672) | G/G | Food allergy | 4 of 13 (30.8%) | p = 0.065 |
G/C | 2 of 13 (15.4%) | |||
C/C | 2 of 2 (100%) | |||
g.40823A>G (rs324015) | A/G | Asthma | 5 of 9 (55.6%) | p = 0.097 |
G/G | 4 of 19 (21.1%) |
Variable | N | PEC Reduction % | EREFS Score Reduction % | |||
---|---|---|---|---|---|---|
Median | IQR | Median | IQR | |||
Histological response | Responders | 15 | 99.23 | 91.67–100.00 | 75.00 | 20.00–80.00 |
Non-responders | 13 | 20.00 $ | −19.65–55.40 | 0.00 * | −25.00–45.00 | |
Sex | Men | 25 | 74.07 | 10–98.37 | 33.33 | 0.00–70.83 |
Women | 3 | 100.00 | - | 100.00 | - | |
Treatment | Omeprazole | 15 | 92.50 $ | 65.71–100.00 | 60.00 | 0.00–80.00 |
Esomeprazole | 4 | −57.14 | −137.50–71.43 | 17.14 | 3.57–80.00 | |
Pantoprazole | 5 | 20.00 | −12.50–61.25 | 0.00 | −50.00–36.67 | |
Lansoprazole | 4 | 62.04 | 12.50–92.94 | 75.00 | −39.58–95.83 | |
Total | 28 | 80.98 | 21.25–99.81 | 36.67 | 0.00–78.75 |
Phenotype or Genotype | N | PEC Reduction % | EREFS Score Reduction % | |||
---|---|---|---|---|---|---|
Median | IQR | Median | IQR | |||
STAT6 g.18453G>C (rs12368672) | G/G | 13 | 87.88 | 12.50–97.12 | 20.00 | 0.00–70.83 |
G/C | 13 | 74.07 | 35.00–100.00 | 66.67 | 7.14–91.67 | |
C/C | 2 | 37.50 | - | −75.00 * | - | |
STAT6 g.27148G>A (rs167769) | G/G | 11 | 91.67 | 56.25–99.23 | 33.33 | 0.00–100.00 |
G/A | 17 | 65.71 | 10.00–100.00 | 40.00 | 0.00–73.33 | |
STAT6 g.28741G>A (rs324011) | G/G | 10 | 93.34 | 38.62–99.42 | 26.67 | 0.00–100.00 |
G/A + A/A | 18 | 69.89 | 10.00–100.00 | 45.00 | 0.00–70.00 | |
STAT6 g.37927C>T (rs841718) | C/C | 3 | 56.25 | - | 0.00 | - |
C/T | 17 | 95.00 | 52.28–100.00 | 66.67 | 20.00–100.00 | |
T/T | 8 | 56.44 | 5.00–91.89 | 7.14 | 0.00–57.50 | |
STAT6 g.38178C>T (rs3024974) | C/C | 19 | 87.88 | 0.00–97.50 | 33.33 | 0.00–66.67 |
C/T | 9 | 74.07 | 55.40–100.00 | 66.67 | −25.00–81.67 | |
STAT6 g.40823A>G (rs324015) | A/G | 9 | 65.71 | −19.65–98.75 | 66.67 | 10.00–100.00 |
G/G | 19 | 87.88 | 25.00–100.00 | 20.00 | 0.00–66.67 | |
STAT6 g.41214A>G (rs1059513) | A/A | 21 | 90.04 | 52.28–100.00 | 50.00 | 0.00–77.50 |
A/G | 7 | 20.00 | −100.00–99.23 | 14.29 | 0.00–100.00 | |
CYP2C19 | RM | 9 | 57.89 | 0.00–93.94 | 40.00 | 0.00–73.33 |
NM | 13 | 91.67 | 5.36–99.62 | 50.00 | 0.00–87.50 | |
IM + PM | 6 | 85.79 | 47.19–100.00 | 16.67 | −12.50–87.50 | |
CYP3A5 | IM | 4 | 95.45 | 63.83–99.81 | 83.33 | 16.67–100.00 |
PM | 24 | 69.89 | 5.00–99.38 | 26.67 | 0.00–72.92 | |
CYP3A4 | *1/*1 | 26 | 80.98 | 15.00–99.43 | 26.67 | 0.00–80.83 |
*1/*22 | 2 | 75.00 | - | 70.83 | - | |
ABCB1 g.167964T>C (rs1128503) | T/T | 6 | 95.02 | 47.19–100.00 | 0.00 | −50.00–56.25 |
T/C | 14 | 61.80 | −6.25–94.38 | 66.67 | 10.71–100.00 | |
C/C | 7 | 74.07 | 0.00–99.23 | 33.33 | 0.00–83.33 | |
ABCB1 g.208920T>C (rs1045642) | T/T | 5 | 56.25 | −2.50–100.00 | −15.28 | −75.00–37.50 |
C/T | 15 | 87.88 | 54.55–100.00 | 66.67 | 20.00–100.00 | |
C/C | 7 | 25.00 | −14.29–99.23 | 14.29 | 0.00–40.00 | |
ABCB1 g.186947T>G/A (rs2032582) | T/T | 4 | 77.87 | 59.85–97.51 | 75.00 | 12.50–100.00 |
T/G | 14 | 93.75 | 47.16–100.00 | 43.33 | 0.00–87.50 | |
G/G+G/A+A/A | 10 | 35.00 | −6.25–90.29 | 26.67 * | −56.25–61.67 | |
TOTAL | 28 | 80.98 | 78.56 | 36.67 | 78.75 |
Gene | Genetic Variant | Allele/s Containing the Variant | TaqMan Assay ID(s) | RefSeq |
---|---|---|---|---|
CYP2C19 | rs4244285 | *2 | C__25986767_70 | NG_008384.3:g.24179G>A |
rs4986893 | *3 | C__27861809_10 | NG_008384.3:g.22973G>A | |
rs28399504 | *4 | C__30634136_10 | NG_008384.3:g.5026A>G | |
rs56337013 | *5 | C__27861810_10 | NG_008384.3:g.95058C>T | |
rs72552267 | *6 | C__27531918_10 | NG_008384.3:g.17773G>A | |
rs72558186 | *7 | C__30634127_10 | NG_008384.3:g.24319T>A | |
rs41291556 | *8 | C__30634130_30 | NG_008384.3:g.17736T>C | |
rs17884712 | *9 | C__25745302_30 | NG_008384.3:g.17809G>A | |
rs12248560 | *17 | C____469857_10 | NG_008384.3:g.4220C>T | |
rs12769205 | *2,*35 | AHWSL0R | NG_008384.3:g.17687A>G | |
CYP3A4 | rs55785340 | *2 | C__30634204_10 | NG_008421.1:g.20826T>C |
rs4986910 | *3 | C__27535825_20 | NG_008421.1:g.28285T>C | |
rs4646438 | *6 | C__32787140_40 | NG_008421.1:g.22774dup | |
rs28371759 | *18 | C__27859823_20 | NG_008421.1:g.25183T>C | |
rs35599367 | *22 | C__59013445_10 | NG_008421.1:g.20493C>T | |
CYP3A5 | rs776746 | *3 | C__26201809_30 | NG_007938.2:g.12083A>G |
rs10264272 | *6 | C__30203950_10 | NG_007938.2:g.19787G>A | |
rs41303343 | *7 | C__32287188_10 | NG_007938.2:g.32228dup | |
ABCB1 | rs1045642 | N/A | C___7586657_20 | NG_011513.1:g.208920T>C |
rs2032582 $ | N/A | C_11711720D_40, C_11711720C_30 | NG_011513.1:g.186947T>G/A | |
rs1128503 | N/A | C___7586662_10 | NG_011513.1:g.167964T>C | |
STAT6 | rs1059513 | N/A | C___7480847_10 | NG_021272.2:g.41214A>G |
rs324015 | N/A | C____620398_10 | NG_021272.2:g.40823A>G | |
rs3024974 | N/A | C__26439023_10 | NG_021272.2:g.38178C>T | |
rs841718 | N/A | C___7480858_10 | NG_021272.2:g.37927C>T | |
rs324011 | N/A | C____620399_10 | NG_021272.2:g.28741G>A | |
rs167769 | N/A | C____620401_20 | NG_021272.2:g.27148G>A | |
rs2598483 | N/A | C__15984966_10 | NG_021272.2:g.24018G>A | |
rs12368672 | N/A | C__31186828_10 | NG_021272.2:g.18453G>C |
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Soria-Chacartegui, P.; Navares-Gómez, M.; Molina-Jiménez, F.; Laserna-Mendieta, E.J.; Arias-González, L.; Majano, P.; Casabona, S.; Lucendo, A.J.; Abad-Santos, F.; Santander, C.; et al. Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis. Int. J. Mol. Sci. 2024, 25, 3685. https://doi.org/10.3390/ijms25073685
Soria-Chacartegui P, Navares-Gómez M, Molina-Jiménez F, Laserna-Mendieta EJ, Arias-González L, Majano P, Casabona S, Lucendo AJ, Abad-Santos F, Santander C, et al. Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis. International Journal of Molecular Sciences. 2024; 25(7):3685. https://doi.org/10.3390/ijms25073685
Chicago/Turabian StyleSoria-Chacartegui, Paula, 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, and et al. 2024. "Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis" International Journal of Molecular Sciences 25, no. 7: 3685. https://doi.org/10.3390/ijms25073685
APA StyleSoria-Chacartegui, P., Navares-Gómez, M., Molina-Jiménez, F., Laserna-Mendieta, E. J., Arias-González, L., Majano, P., Casabona, S., Lucendo, A. J., Abad-Santos, F., Santander, C., & Zubiaur, P. (2024). Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis. International Journal of Molecular Sciences, 25(7), 3685. https://doi.org/10.3390/ijms25073685