Association between ADAM33 Single-Nucleotide Polymorphisms and Treatment Response to Inhaled Corticosteroids and a Long-Acting Beta-Agonist in Asthma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Genomic DNA Isolation
2.3. SNP Genotyping
2.4. Analysis of SNPs of the ADAM33 Gene
2.5. Statistical Analysis
3. Results
3.1. Demographic and Clinical Profiles of the Study Population
3.2. Improvement in Lung Function in Various Severity Groups upon ICS and LABA Treatment
3.3. ADAM33 SNP Distribution in the Study Population
3.4. ADAM33 SNP Association with Disease Severity
3.5. ADAM33 SNP Association with Lung Function Improvement in Asthma Patients upon ICS and LABA Treatment
3.6. Haplotype Association of ADAM33 SNPs with Asthma
4. Discussion
Strength and Limitations
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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Controls (N = 486) | Asthma Patients (N = 503) | |
---|---|---|
Age | ||
≤40 years | 291 (59.8) | 305 |
>40 years | 195 | 198 |
Gender | ||
Male | 252 | 253 |
Female | 234 | 250 |
Smoking status | ||
Smoker | - | 57 |
Non-Smoker | 486 | 446 |
Family History of Asthma | ||
Yes | - | 213 |
No | - | 290 |
Asthma Duration | ||
<1 year | - | 61 |
1–5 years | - | 196 |
>5 years | - | 246 |
Severity according to GINA guidelines | ||
Mild persistent | - | 125 (24.9%) |
Moderate persistent | - | 212 (42.3%) |
Severe persistent | - | 166 (32.8%) |
Number of Allergens Sensitized | ||
≤5 | - | 246 |
>5 | - | 257 |
Wheal diameter | ||
≤Histamine | - | 307 |
>Histamine | - | 196 |
Pulmonary Function Test | Controls | Asthma Patients | |
---|---|---|---|
Pre-Bronchodilator | Pre-Bronchodilator | Post-Bronchodilator | |
FVC (% pred) | 88.44 ± 0.511 | 70.53 ± 0.82 | 76.02 ± 0.79 |
FEV1 (% pred) | 88.84 ± 0.47 | 66.96 ± 0.89 | 74.23 ± 0.90 |
FEV1/FVC (% pred) | 104.23 ± 0.35 | 96.69 ± 0.62 | 102.0 ± 0.66 |
PEF (L/s) | 92.81 ± 0.95 | 71.60 ± 1.0 | 77.96 ± 1.05 |
Baseline | Follow-Up (Three Months after ICS+LABAs) | |||||
---|---|---|---|---|---|---|
Genotype | Asthma Patients | Mean ± SE of Baseline Predicted FVC (%) | 95% CI Lower and Upper Limits | Mean ± SE of FVC (%) | 95% CI Lower and Upper Limits | |
rs2280091 | AA | 353 | 70.3 ± 0.952 | 68.4–72.2 | 75.8 ± 0.916 | 74.0–77.6 |
GA | 129 | 70.0 ± 1.70 | 66.7–73.4 | 75.0 ± 1.596 | 71.8–78.2 | |
GG | 21 | 77.2 ± 4.78 | 67.3–87.2 | 82.0 ± 4.72 | 72.2–91.8 | |
p-value | 0.293 | 0.141 | ||||
rs2787094 | GG | 269 | 70.5 ± 1.15 | 68.3–72.8 | 76.2 ± 1.05 | 74.1–78.2 |
GC | 196 | 71.8 ± 1.28 | 69.3–74.3 | 76.8 ± 1.27 | 74.3–79.3 | |
CC | 38 | 64.1 ± 2.88 | 58.2–69.9 | 68.4 ± 2.92 | 62.5–74.4 | |
p-value | 0.043 | 0.048 | ||||
rs3918396 | GG | 389 | 70.5 ± 0.945 | 68.7–72.4 | 75.8 ± 0.891 | 74.1–77.6 |
GA | 107 | 71.0 ± 1.72 | 67.6–74.4 | 76.8 ± 1.75 | 73.1–79.9 | |
AA | 7 | 62.4 ± 7.14 | 45.0–79.9 | 67.4 ± 7.51 | 49.1–85.8 | |
p-value | 0.442 | 0.222 | ||||
rs677044 | AA | 327 | 70.4 ± 0.990 | 68.5–72.4 | 76.1 ± 0.945 | 74.1–77.8 |
AG | 155 | 70.8 ± 1.58 | 67.7–73.9 | 75.7 ± 1.540 | 72.7–78.7 | |
GG | 21 | 70.0 ± 4.14 | 61.4–78.6 | 75.2 ± 3.349 | 68.2–82.2 | |
p-value | 0.913 | 0.964 | ||||
rs2853209 | AA | 247 | 71.1 ± 1.06 | 69.0–73.2 | 77.1 ± 1.07 | 75.0–79.2 |
AT | 195 | 70.4 ± 1.40 | 67.7–73.2 | 74.9 ± 1.31 | 72.4–77.5 | |
TT | 61 | 68.5 ± 2.80 | 62.9–74.1 | 74.0 ± 2.50 | 69.0–79.0 | |
p-value | 0.969 | 0.374 | ||||
rs3918392 | AA | 435 | 70.3 ± 0.908 | 68.5–72.1 | 75.8 ± 0.853 | 74.2–77.5 |
AG | 64 | 72.0 ± 1.897 | 68.2–75.8 | 76.2 ± 2.157 | 71.9–80.5 | |
GG | 4 | 72.8 ± 7.962 | 47.4–98.1 | 72.5 ± 6.035 | 53.3–91.7 | |
p-value | 0.822 | 0.847 |
Baseline | Follow-Up (Three Months after ICS+LABAs) | |||||
---|---|---|---|---|---|---|
Genotype | Asthma Patients | Mean ± SE of Baseline Predicted FEV1 (%) | 95% CI Lower and Upper Limits | Mean ± SE of FEV1 (%) | 95% CI Lower and Upper Limits | |
rs2280091 | AA | 353 | 66.3 ± 1.061 | 64.2–68.4 | 74.2 ± 1.10 | 72.0–76.3 |
GA | 129 | 67.7 ± 1.780 | 64.1–71.2 | 73.6 ± 1.62 | 70.4–76.8 | |
GG | 21 | 73.6 ± 4.776 | 63.6–83.5 | 78.4 ± 4.54 | 68.9–87.8 | |
p-value | 0.314 | 0.459 | ||||
rs2787094 | GG | 269 | 66.9 ± 1.23 | 64.5–69.3 | 74.1 ± 1.16 | 71.8–76.3 |
GC | 196 | 68.5 ± 1.39 | 65.8–71.3 | 75.9 ± 1.47 | 73.0–78.8 | |
CC | 38 | 59.1 ± 3.48 | 52.1–66.2 | 66.4 ± 3.78 | 58.8–74.1 | |
p-value | 0.038 | 0.049 | ||||
rs3918396 | GG | 389 | 66.8 ± 1.027 | 64.8–68.8 | 73.7 ± 0.990 | 71.7–75.7 |
GA | 107 | 67.9 ± 1.890 | 64.1–71.6 | 76.0 ± 2.14 | 71.7–80.2 | |
AA | 7 | 63.4 ± 8.454 | 42.7–84.1 | 73.6 ± 6.37 | 58.0–89.2 | |
p-value | 0.746 | 0.421 | ||||
rs677044 | AA | 327 | 66.7 ± 1.063 | 64.6–68.8 | 74.6 ± 1.10 | 72.4–76.7 |
AG | 155 | 67.4 ± 1.725 | 64.0–70.8 | 73.4 ± 1.64 | 70.2–76.7 | |
GG | 21 | 67.6 ± 5.187 | 56.8–78.4 | 74.2 ± 4.58 | 64.6–83.7 | |
p-value | 0.676 | 0.978 | ||||
rs2853209 | AA | 247 | 66.5 ± 1.19 | 64.2–68.9 | 76.7 ± 1.30 | 74.1–79.3 |
AT | 195 | 68.0 ± 1.48 | 65.1–70.9 | 72.4 ± 1.36 | 69.7–75.0 | |
TT | 61 | 65.3 ± 3.02 | 59.3–71.4 | 69.9 ± 2.62 | 64.7–75.1 | |
p-value | 0.722 | 0.040 | ||||
rs3918392 | AA | 435 | 66.7 ± 0.975 | 64.7–68.6 | 74.0 ± 0.969 | 72.1–75.9 |
AG | 64 | 69.2 ± 2.307 | 64.5–73.8 | 75.6 ± 2.37 | 70.8–80.3 | |
GG | 4 | 64.3 ± 11.842 | 26.6–101.9 | 70.3 ± 11.9 | 32.4–108.1 | |
p-value | 0.631 | 0.826 |
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Vishweswaraiah, S.; Ramachandra, N.B.; Joshi, N.; Parthasarathi, A.; Kaleem Ullah, M.; Siddaiah, J.B.; Holla, A.D.; Chakraborty, S.; Agrawal, A.; Mahesh, P.A. Association between ADAM33 Single-Nucleotide Polymorphisms and Treatment Response to Inhaled Corticosteroids and a Long-Acting Beta-Agonist in Asthma. Diagnostics 2023, 13, 405. https://doi.org/10.3390/diagnostics13030405
Vishweswaraiah S, Ramachandra NB, Joshi N, Parthasarathi A, Kaleem Ullah M, Siddaiah JB, Holla AD, Chakraborty S, Agrawal A, Mahesh PA. Association between ADAM33 Single-Nucleotide Polymorphisms and Treatment Response to Inhaled Corticosteroids and a Long-Acting Beta-Agonist in Asthma. Diagnostics. 2023; 13(3):405. https://doi.org/10.3390/diagnostics13030405
Chicago/Turabian StyleVishweswaraiah, Sangeetha, Nallur B. Ramachandra, Neha Joshi, Ashwaghosha Parthasarathi, Mohammed Kaleem Ullah, Jayaraj Biligere Siddaiah, Amrutha D. Holla, Samarpana Chakraborty, Anurag Agrawal, and Padukudru Anand Mahesh. 2023. "Association between ADAM33 Single-Nucleotide Polymorphisms and Treatment Response to Inhaled Corticosteroids and a Long-Acting Beta-Agonist in Asthma" Diagnostics 13, no. 3: 405. https://doi.org/10.3390/diagnostics13030405