Association between ADCY9 Gene Polymorphisms and Ritodrine Treatment Outcomes in Patients with Preterm Labor
Abstract
:1. Introduction
2. Methods
2.1. Patients
2.2. Drug Administration
2.3. Outcomes and Data Collection
2.4. Selection of Single Nucleotide Polymorphisms (SNPs)
2.5. Genotyping Methods
2.6. Statistical Analyses
2.7. In Silico Analyses
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | Number of Patients | Time to Delivery Median (95% CI) | p Value |
---|---|---|---|
Age (years) | |||
<30 | 59 | 1168.6 (764.3–1572.8) | 0.492 |
≥30 | 104 | 1040.0 (670.5–1409.5) | |
Height (cm) | |||
<160 | 53 | 1027.2 (580.6–1473.7) | 0.419 |
≥160 | 110 | 1168.6 (873.7–1463.4) | |
Weight (kg) | |||
<60 | 66 | 978.6 (476.1–1481.0) | 0.983 |
≥60 | 97 | 1230.6 (964.5–1496.7) | |
BMI (kg/m2) | |||
<25 | 112 | 1247.8 (940.7–1554.9) | 0.934 |
≥25 | 51 | 1040.0 (656.0–1424.0) | |
Gestational age at drug therapy (weeks) | |||
<32 | 111 | 1408.1 (1172.8–1643.5) | <0.001 |
≥32 | 52 | 548.0 (272.0–824.0) | |
Modified Bishop score a | |||
<3 | 109 | 1247.8 (1112.9–1382.8) | 0.001 |
≥3 | 19 | 156.9 (25.5–288.3) | |
Multiple pregnancy b | 0.207 | ||
Single | 125 | 1072.6 (800.2–1345.1) | |
Multiple | 18 | 631.1 (147.2–1114.9) |
Gene Polymorphism | Minor Allele Frequency (%) | Grouped Genotype | Number of Patients | Time to Delivery Median (95% CI) | p Value |
---|---|---|---|---|---|
ADCY9 | |||||
rs879619 (C > T) a | 27.4 | CC | 82 | 811.6 (532.9–1090.4) | 0.018 |
CT, TT | 79 | 1300.8 (1187.1–1414.5) | |||
rs2601796 (C > T) a | 7.6 | CC, CT | 24 | 978.6 (495.4–1461.7) | 0.650 |
TT | 137 | 1168.6 (874.4–1462.7) | |||
rs2531988 (T > G) | 28.6 | TT, GT | 83 | 1275.4 (974.3–1576.4) | 0.565 |
GG | 80 | 934.7 (679.5–1190.0) | |||
rs2531995 (C > T) | 35.0 | CC, CT | 147 | 1190.7 (961.0–1420.4) | 0.039 |
TT | 16 | 613.9 (0–1237.0) | |||
rs2230739 (T > C) b | 38.2 | TT, CT | 142 | 1168.6 (940.2–1396.9) | 0.340 |
CC | 20 | 613.9 (42.4–1185.5) | |||
PDE4B | |||||
rs598961 (G > A) c | 37.1 | GG, GA | 89 | 1298.9 (1162.2–1435.7) | 0.102 |
AA | 58 | 828.6 (553.3–1103.9) | |||
ADRB2 | |||||
rs1042719 (G > C) b | 44.5 | GG | 53 | 1338.5 (950.1–1727.0) | 0.012 |
GC,CC | 109 | 978.6 (680.5–1276.6) | |||
ADCY9/PDE4B/ADRB2 | |||||
rs879619/rs598961/rs1042719 d | N/A | CC/AA/ GC,CC | 20 | 568.6 (0–1261.9) | 0.004 |
Others | 125 | 1274.8 (1077.3–1432.2) | |||
rs2531995/rs598961/rs1042719 c | N/A | CC,CT/GG,GA/GG | 25 | 1875.5 (1084.2–2666.8) | <0.001 |
Others | 122 | 978.6 (738.4–1218.7) |
Factor | Model I | Model II | Model III |
---|---|---|---|
Adjusted HR (95% CI) | Adjusted HR (95% CI) | Adjusted HR (95% CI) | |
Gestational age at drug therapy (≥32 weeks) | 4.0 (2.4–6.9) *** | 4.7 (2.7–8.3) *** | 4.1 (2.3–7.3) *** |
Modified Bishop score (≥ 3) | 2.1 (1.2–3.9) * | 2.2 (1.2–4.1) * | 2.3 (1.2–4.3) * |
ADRB2 rs1042719 (GC,CC) | 1.6 (1.0–2.6) | ||
ADCY9 rs879619 (CC) | 2.0 (1.3–3.2) ** | 2.1 (1.3–3.3) ** | |
ADCY9 rs879619/PDE4B rs598961 /ADRB2 rs1042719(CC/AA/GC,CC) | 3.2 (1.7–6.3) ** | ||
ADCY9 rs2531995/PDE4B rs598961 /ADRB2 rs1042719 (CC,CT/GG,GA/GG) | 0.4 (0.2–0.7) ** |
Characteristic | Number of Patients (%) | Adverse Drug Events | p Value | |
---|---|---|---|---|
Yes (n = 46) | No (n = 117) | |||
Age (years) | ||||
<30 | 59 (36.2) | 15 (32.6) | 44 (37.6) | 0.550 |
≥30 | 104 (63.8) | 31 (67.4) | 73 (62.4) | |
Mean ± S.D | 31.0 ± 3.7 | 31.0 ± 4.4 | 30.9 ± 3.5 | 0.880 |
Height (cm) | ||||
<160 | 53 (32.5) | 22 (47.8) | 31 (26.5) | 0.009 |
≥160 | 110 (67.5) | 24 (52.2) | 86 (73.5) | |
Mean ± S.D | 161.2 ± 4.5 | 160.3 ± 4.7 | 161.6 ± 4.4 | 0.083 |
Weight (kg) | ||||
<60 | 66 (40.5) | 24 (52.2) | 42 (35.9) | 0.057 |
≥60 | 97 (59.5) | 22 (47.8) | 75 (64.1) | |
Mean ± S.D | 62.5 ± 8.5 | 61.0 ± 8.2 | 63.0 ± 8.6 | 0.176 |
BMI (kg/m2) | ||||
<25 | 112 (68.7) | 33 (71.7) | 79 (67.5) | 0.601 |
≥25 | 51 (31.3) | 13 (28.3) | 38 (32.5) | |
Mean ± S.D | 24.0 ± 3.0 | 23.7 ± 2.8 | 24.1 ± 3.2 | 0.458 |
Gestational age at drug therapy(weeks) | ||||
<32 | 111 (68.1) | 33 (71.7) | 78 (66.7) | 0.532 |
≥32 | 52 (31.9) | 13 (28.3) | 39 (33.3) | |
Mean ± S.D | 29.7 ± 3.7 | 29.0 ± 3.9 | 29.9 ± 3.6 | 0.151 |
Modified Bishop score a | ||||
<3 | 109 (85.2) | 32 (91.4) | 77 (82.8) | 0.221 |
≥3 | 19 (14.8) | 3 (8.6) | 16 (17.2) | |
Multiple pregnancy b | 0.098 | |||
Single | 125 (87.4) | 35 (79.5) | 90 (90.9) | |
Multiple | 18 (12.6) | 9 (20.5) | 9 (9.1) | |
rs879619 (C > T) c | ||||
CC | 82 (50.9) | 22 (47.8) | 60 (52.2) | 0.618 |
CT, TT | 79 (49.1) | 24 (52.2) | 55 (47.8) | |
rs2601796 (C > T) c | ||||
CC, CT | 24 (14.9) | 7 (15.6) | 17 (14.7) | 0.886 |
TT | 137 (85.1) | 38 (84.4) | 99 (85.3) | |
rs2531988 (T > G) | ||||
TT, GT | 83 (50.9) | 22 (47.8) | 61 (52.1) | 0.620 |
GG | 80 (49.1) | 24 (52.2) | 56 (47.9) | |
rs2531995 (C > T) | ||||
CC | 64 (39.3) | 25 (54.3) | 39 (33.3) | 0.013 |
CT, TT | 99 (60.7) | 21 (45.7) | 78 (66.7) | |
rs2230739 (T > C) d | ||||
TT | 66 (40.7) | 21 (45.7) | 45 (38.8) | 0.423 |
CT, CC | 96 (59.3) | 25 (54.3) | 71 (61.2) | |
PDE4B rs598961 (G > A) e | ||||
GG, GA | 89 (60.5) | 20 (52.6) | 69 (63.3) | 0.246 |
AA | 58 (39.5) | 18 (47.4) | 40 (36.7) | |
ADRB2 rs1042719 (G > C) d | ||||
GG, GC | 125 (77.2) | 37 (82.2) | 88 (75.2) | 0.341 |
CC | 37 (22.8) | 8 (17.8) | 29 (24.8) | |
ADCY9/ADRB2 rs2531995/rs1042719 d | ||||
CC/GG,GC | 16 (9.9) | 8 (17.8) | 8 (6.8) | 0.073 |
Others | 146 (90.1) | 37 (82.2) | 109 (93.2) |
Factor | Unadjusted OR (95% CI) | Adjusted OR (95% CI) |
---|---|---|
Age (≥ 30) | 1.2 (0.6–2.6) | |
Height (< 160 cm) | 2.5 (1.1–5.2) * | 2.5 (1.2–5.2) * |
ADRB2 rs1042719 (GG,GC) | 1.5 (0.6–3.6) | |
ADCY9 rs2531995 (CC) | 2.4 (1.2–4.8) * | 2.2 (1.1–4.2) * |
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Lee, N.; Yoon, H.-Y.; Park, J.-Y.; Kim, Y.-J.; Hwang, H.-S.; Yee, J.; Gwak, H.-S. Association between ADCY9 Gene Polymorphisms and Ritodrine Treatment Outcomes in Patients with Preterm Labor. Pharmaceutics 2021, 13, 1653. https://doi.org/10.3390/pharmaceutics13101653
Lee N, Yoon H-Y, Park J-Y, Kim Y-J, Hwang H-S, Yee J, Gwak H-S. Association between ADCY9 Gene Polymorphisms and Ritodrine Treatment Outcomes in Patients with Preterm Labor. Pharmaceutics. 2021; 13(10):1653. https://doi.org/10.3390/pharmaceutics13101653
Chicago/Turabian StyleLee, Nari, Ha-Young Yoon, Jin-Young Park, Young-Ju Kim, Han-Sung Hwang, Jeong Yee, and Hye-Sun Gwak. 2021. "Association between ADCY9 Gene Polymorphisms and Ritodrine Treatment Outcomes in Patients with Preterm Labor" Pharmaceutics 13, no. 10: 1653. https://doi.org/10.3390/pharmaceutics13101653
APA StyleLee, N., Yoon, H.-Y., Park, J.-Y., Kim, Y.-J., Hwang, H.-S., Yee, J., & Gwak, H.-S. (2021). Association between ADCY9 Gene Polymorphisms and Ritodrine Treatment Outcomes in Patients with Preterm Labor. Pharmaceutics, 13(10), 1653. https://doi.org/10.3390/pharmaceutics13101653