Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Genetic Variant Analysis
2.3. DNA Sequencing
2.4. Bioinformatic Analysis
2.5. Statistical Analysis
3. Results
3.1. Population Sample Characteristics
3.2. Genetic Variant Detection
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
Abbreviations
PDA | Patent ductus arteriosus |
EPAS1 | Endothelial PAS domain protein 1 |
SNP | Single-nucleotide polymorphism |
OR | Odds ratio |
HRM | High-resolution melting |
HSF | Human splicing finder |
ACGM | American College of Medical Genetics and Genomics |
COX | Cyclooxygenase |
TFAP2B | Transcription factor AP-2 beta |
HIF | Hypoxia-inducible factor |
PHD | Prolyl hydroxylase |
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Control | Case | p | ||
---|---|---|---|---|
Mother | ||||
Hypertension n (%) | 9 (32.1) | 7 (36.8) | 0.763 | |
Preeclampsia n (%) | 9 (32.1) | 5 (26.3) | 0.753 | |
T2D n (%) | 4 (14.3) | 0 | 0.137 | |
Prenatal infections n (%) | 12(42.9) | 9 (47.4) | 0.775 | |
Prenatal treatment | Indomethacin n (%) | 0 | 1 (5.3) | 0.404 |
Steroid n (%) | 20 (76.9) | 13 (68.4) | 0.734 | |
Newborn | ||||
Sex F/M n | 9/19 | 8/11 | 0.546 | |
Gestational age | 30 ± 2.3 | 28.8 ± 2.8 | 0.112 | |
Birth weight (g) | 1229 ± 349 | 928 ± 154 | <0.0001 | |
Ductal diameter (mm) | 2.9 ± 0.9 | 2.9 ± 0.8 | 0.765 | |
Sepsis n (%) | 16 (57.1) | 1 (5.3) | <0.0001 | |
Early n (%) | 7 (25) | 0 | 0.032 | |
Late n (%) | 10 (35.7) | 0 | 0.003 |
Genotype Frequency (%) | TFAP2B | Allelic Frequency (%) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
9757AT | A/A | A/T | T/T | p * | A | T | p ** | ORc | (IC 95%) | p HW |
Control (n = 28) | 23 (82) | 5 (18) | 0 (0) | 51 (91) | 5 (9) | 1 | ||||
Case (n = 19) | 19 (100) | 0 (0) | 0 (0) | 0.018 | 38 (100) | 0 (0) | 0.0032 | - | - | 1 |
29461AT | A/A | A/T | T/T | A | T | |||||
Control (n = 28) | 24 (85.7) | 4 (14.3) | 0 (0) | 52 (93) | 4 (7) | 1 | ||||
Case (n = 19) | 17 (89.5) | 2 (10.5) | 0 (0) | 0.70 | 36 (95) | 2 (5) | 0.767 | 0.699 | 0.21–2.28 | 1 |
EPAS1 | ||||||||||
rs7557402 | C/C | C/G | G/G | C | G | |||||
Control (n = 28) | 24 (85.7) | 4 (14.3) | 0 (0) | 52 (93) | 4 (7) | 1 | ||||
Case (n = 19) | 14 (73.7) | 2 (10.5) | 3 (15.8) | 0.05 | 30 (79) | 8 (21) | 0.007 | 3.53 | 1.42–8.74 | 0.0096 |
54455C>T | C/C | C/T | T/T | C | T | |||||
Control (n = 28) | 24 (85.7) | 4 (14.3) | 0 (0) | 52 (93) | 4 (7) | 1 | ||||
Case (n = 19) | 17 (89.5) | 1 (5.3) | 1 (5.3) | 0.25 | 35 (92) | 3 (8) | 1 | 1.15 | 0.402–3.31 | 0.08 |
54522G>A | G/G | G/A | A/A | G | A | |||||
Control (n = 28) | 24 (85.7) | 1 (3.6) | 3 (10.7) | 49 (88) | 7 (12) | 0.0007 | ||||
Case (n = 19) | 16 (84.2) | 0 (0) | 3 (15.8) | 0.53 | 32 (84) | 6 (16) | 0.541 | 1.39 | 0.62–3.12 | 0.0003 |
rs769385664 | G/G | G/A | A/A | G | A | |||||
Control (n = 28) | 26 (92.6) | 1 (3.6) | 1 (3.6) | 53 (95) | 3 (5) | 0.055 | ||||
Case (n = 19) | 16 (84.2) | 3 (15.8) | 0 (0) | 0.21 | 35 (92) | 3 (8) | 0.567 | 1.65 | 0.521–5.23 | 1 |
54699C>A | C/C | C/A | A/A | C | A | |||||
Control (n = 28) | 21 (75) | 5 (17.9) | 2 (7.1) | 47 (84) | 9 (16) | 0.11 | ||||
Case (n = 19) | 13 (68.4) | 4 (21.1) | 2 (10.5) | 0.87 | 30 (79) | 8 (21) | 0.466 | 1.39 | 0.679–2.86 | 0.14 |
54700A>C | A/A | A/C | C/C | A | C | |||||
Control (n = 28) | 22 (78.6) | 5 (17.9) | 1 (3.6) | 49 (88) | 7 (12) | 0.35 | ||||
Case (n = 19) | 14 (73.7) | 4 (21.1) | 1 (5.3) | 0.92 | 32 (84) | 6 (16) | 0.541 | 1.39 | 0.623–3.127 | 0.37 |
54701G>C | G/G | G/C | C/C | G | C | |||||
Control (n = 28) | 19 (67.9) | 8 (28.6) | 1 (3.6) | 46 (82) | 10 (18) | 1 | ||||
Case (n = 19) | 14 (73.7) | 5 (26.3) | 0 (0) | 0.57 | 33 (87) | 5 (13) | 0.434 | 0.68 | 0.313–1.476 | 1 |
rs1286681984 | C/C | C/A | A/A | C | A | |||||
Control (n = 28) | 24 (85.7) | 4 (14.3) | 0 (0) | 52 (93) | 4 (7) | 1 | ||||
Case (n = 19) | 16 (84.2) | 2 (10.5) | 1 (5.3) | 0.38 | 34 (89) | 4 (11) | 0.459 | 1.64 | 0.61–4.42 | 0.16 |
54703C>G | C/C | C/G | G/G | C | G | |||||
Control (n = 28) | 24 (85.7) | 4 (14.3) | 0 (0) | 52 (93) | 4 (7) | 1 | ||||
Case (n = 19) | 17 (89.5) | 2 (10.5) | 0 (0) | 0.7 | 36 (95) | 2 (5) | 0.767 | 0.699 | 0.21–2.28 | 1 |
54707C>G | C/C | C/G | G/G | C | G | |||||
Control (n = 28) | 25 (89.3) | 3 (10.7) | 0 (0) | 53 (95) | 3 (5) | 1 | ||||
Case (n = 19) | 17 (89.5) | 2 (10.5) | 0 (0) | 0.98 | 36 (95) | 2 (5) | 1 | 1 | 0.28–3.56 | 1 |
rs762559920 | G/G | G/C | C/C | G | C | |||||
Control (n = 28) | 27 (96.4) | 1 (3.6) | 0 (0) | 55 (98) | 1 (2) | 1 | ||||
Case (n = 19) | 16 (84.2) | 3 (15.8) | 0 (0) | 0.14 | 35 (92) | 3 (8) | 0.1 | 4.26 | 0.88–20.59 | 1 |
Model | Genotype | Case | Control | OR (95% CI) | p Value |
---|---|---|---|---|---|
Codominant | C/C | 14 (73.7%) | 24 (85.7%) | 0.056 | |
C/G | 2 (10.5%) | 4 (14.3%) | 1.17 (0.19–7.21) | ||
G/G | 3 (15.8%) | 0 (0%) | 0.00 (0.00-NA) | ||
Dominant | C/C | 14 (73.7%) | 24 (85.7%) | 0.31 | |
C/G-G/G | 5 (26.3%) | 4 (14.3%) | 0.47 (0.11–2.03) | ||
Recessive | C/C-C/G | 16 (84.2%) | 28 (100%) | 0.017 | |
G/G | 3 (15.8%) | 0 (0%) | 0.00 (0.00-NA) | ||
Overdominant | C/C-G/G | 17 (89.5%) | 24 (85.7%) | 1 | 0.7 |
C/G | 2 (10.5%) | 4 (14.3%) | 1.42 (0.23–8.64) | ||
Additive | - | - | - | 0.41 (0.13–1.26) | 0.098 |
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Rogel-Ayala, D.G.; Muñoz-Medina, J.E.; Vicente-Juárez, V.D.; Grether-González, P.; Morales-Barquet, D.A.; Martínez-García, A.d.J.; Echaniz-Aviles, M.O.L.; Sevilla-Montoya, R.; Martínez-Juárez, A.; Artega-Vázquez, J.; et al. Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen. Diagnostics 2023, 13, 2558. https://doi.org/10.3390/diagnostics13152558
Rogel-Ayala DG, Muñoz-Medina JE, Vicente-Juárez VD, Grether-González P, Morales-Barquet DA, Martínez-García AdJ, Echaniz-Aviles MOL, Sevilla-Montoya R, Martínez-Juárez A, Artega-Vázquez J, et al. Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen. Diagnostics. 2023; 13(15):2558. https://doi.org/10.3390/diagnostics13152558
Chicago/Turabian StyleRogel-Ayala, Diana G., José Esteban Muñoz-Medina, Valeria Dejanira Vicente-Juárez, Patricia Grether-González, Deneb Algedi Morales-Barquet, Alfonso de Jesús Martínez-García, María Olga Leticia Echaniz-Aviles, Rosalba Sevilla-Montoya, Alejandro Martínez-Juárez, Jazmin Artega-Vázquez, and et al. 2023. "Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen" Diagnostics 13, no. 15: 2558. https://doi.org/10.3390/diagnostics13152558