Background
Methods
Subjects
Genotyping
Statistics
Results
Characteristics of the study subjects
ATA | AERD | P | |
---|---|---|---|
N | 995 | 141 | – |
Sex (male, %) | 38.5% | 38.3% | 0.965 |
Age (yr) | 44.8 ± 0.49 | 42.39 ± 1.26 | 0.082 |
Age of onset (yr) | 38.82 ± 0.53 | 34.5 ± 1.53 | 0.007 |
Smoking status (NS/ES/SM, %) | 69.6/16.6/13.7 | 79.4/5.0/15.6 | 0.002 |
Body mass index (kg/m2) | 24.38 ± 0.11 | 23.65 ± 0.3 | 0.023 |
FEV1 before ASA challenge (% predicted) | 83.42 ± 0.63 | 80.52 ± 1.76 | 0.124 |
Decline of FEV1 after ASA challenge (%) | 3.83 ± 0.16 | 32.42 ± 1.08 | 1.14× 10−53
|
log(PC20 methacholine (mg/mL)) | 0.36 ± 0.02 | −0.02 ± 0.07 | 1.13× 10−7
|
Atopy (Y, %) | 51.9% | 48.2% | 0.419 |
Serum total IgE (kU/L) | 393.02 ± 20.22 | 411.2 ± 60.71 | 0.768 |
Urticaria (Y, %) | 22.0% | 19.9% | 0.562 |
Water’s view (Y, %) | 34.7% | 59.6% | 1.14× 10−8
|
Peripheral eosinophil count | 119.88 ± 4.72 | 112.2 ± 13.97 | 0.603 |
Sputum eosinophil (%) | 33.37 ± 1.26 | 32.65 ± 3.83 | 0.858 |
Sputum neutrophil (%) | 5.66 ± 0.51 | 11.35 ± 2.31 | 0.018 |
Frequency, heterozygosity, and the Hardy–Weinberg equilibrium of SNPs in ILVBL
Associations between ILVBL polymorphisms and the risk for and phenotypes of AERD in asthmatics
Locus | Allele | Location | MAF | OR [95% CI] | P*
| Pcorr
**
| |
---|---|---|---|---|---|---|---|
AERD | ATA | ||||||
rs2074267
|
C > A
| 5’-UTR | 0.358 | 0.414 | 0.79 [0.61–1.03] | 0.076 | 0.699 |
rs4141356
|
G > A
| 5’-UTR | 0.447 | 0.378 | 1.33 [1.03–1.71] | 0.027 | 0.250 |
rs718100
|
T > G
| intron 2 | 0.429 | 0.344 | 1.44 [1.11–1.85] | 0.005 | 0.046 |
rs2074265
|
C > A
| Exon 6 (L213 L) | 0.433 | 0.348 | 1.43 [1.11–1.84] | 0.005 | 0.049 |
rs2240299
|
T > C
| intron 9 | 0.241 | 0.352 | 0.58 [0.44–0.78] | 2.28 × 10−4
| 0.002 |
rs7507755
|
G > A
| intron 10 | 0.241 | 0.352 | 0.59 [0.44–0.78] | 2.38 × 10−4
| 0.002 |
rs1468198
|
C > T
| intron 10 | 0.475 | 0.603 | 0.60 [0.46–0.77] | 6.11 × 10−5
| 0.001 |
rs2074261
|
C > A
| intron 14 | 0.379 | 0.501 | 0.61 [0.47–0.79] | 1.41 × 10−4
| 0.001 |
rs13301
|
T > C
| 3′-flanking | 0.387 | 0.502 | 0.63 [0.48–0.81] | 2.82 × 10−4
| 0.003 |
BL1ht1
|
CAGA
| – | 0.316 | 0.371 | 0.78 [0.60–1.02] | 0.072 | 0.580 |
BL1ht3
|
AAGA
| – | 0.220 | 0.242 | 0.88 [0.65–1.19] | 0.410 | 1.000 |
BL1ht4
|
CGGA
| – | 0.032 | 0.037 | 0.86 [0.43–1.75] | 0.684 | 1.000 |
BL2ht3
|
CATCT
| – | 0.135 | 0.146 | 0.91 [0.63–1.31] | 0.608 | 1.000 |
BL2ht4
|
CATAC
| – | 0.021 | 0.028 | 0.75 [0.32–1.76] | 0.508 | 1.000 |
Locus | Diag | Genotype | Codominant. | Dominant. | Recessive | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
RR | CR | CC | Total | OR [95% CI] | P*
| Pcorr
**
| OR [95% CI] | P*
| Pcorr
**
| OR [95% CI] | P*
| Pcorr
**
| ||
rs2074267
| AERD | 20 (14.2%) | 61 (43.3%) | 60 (42.6%) | 141 (100%) | 0.79 [0.61–1.04] | 0.087 | 0.799 | 0.67 [0.47–0.96] | 0.030 | 0.273 | 0.91 [0.55–1.52] | 0.729 | 1.000 |
ATA | 153 (15.4%) | 517 (52.0%) | 325 (32.7%) | 995 (100%) | ||||||||||
rs4141356
| AERD | 31 (22.0%) | 64 (45.4%) | 46 (32.6%) | 141 (100%) | 1.33 [1.04–1.72] | 0.026 | 0.235 | 1.3 [0.89–1.89] | 0.174 | 1.000 | 1.73 [1.12–2.69] | 0.014 | 0.131 |
ATA | 140 (14.1%) | 473 (47.5%) | 382 (38.4%) | 995 (100%) | ||||||||||
rs718100
| AERD | 30 (21.3%) | 61 (43.3%) | 50 (35.5%) | 141 (100%) | 1.43 [1.11–1.85] | 0.006 | 0.050 | 1.38 [0.95–1.99] | 0.089 | 0.819 | 2.04 [1.30–3.20] | 0.002 | 0.017 |
ATA | 116 (11.7%) | 452 (45.4%) | 427 (42.9%) | 995 (100%) | ||||||||||
rs2074265
| AERD | 30 (21.3%) | 62 (44.0%) | 49 (34.8%) | 141 (100%) | 1.43 [1.11–1.84] | 0.006 | 0.055 | 1.39 [0.96–2.01] | 0.081 | 0.745 | 1.98 [1.27–3.11] | 0.003 | 0.026 |
ATA | 119 (12.0%) | 454 (45.6%) | 422 (42.4%) | 995 (100%) | ||||||||||
rs2240299
| AERD | 7 (5.0%) | 54 (38.3%) | 80 (56.7%) | 141 (100%) | 0.59 [0.45–0.79] | 3.65 × 10−4
| 0.003 | 0.57 [0.4–0.82] | 0.002 | 0.020 | 0.34 [0.16–0.75] | 0.007 | 0.068 |
ATA | 131 (13.2%) | 438 (44.1%) | 425 (42.8%) | 994 (100%) | ||||||||||
rs7507755
| AERD | 7 (5.0%) | 54 (38.3%) | 80 (56.7%) | 141 (100%) | 0.59 [0.45–0.79] | 3.78 × 10−4
| 0.003 | 0.57 [0.4–0.82] | 0.002 | 0.021 | 0.34 [0.16–0.75] | 0.008 | 0.069 |
ATA | 131 (13.2%) | 438 (44.0%) | 426 (42.8%) | 995 (100%) | ||||||||||
rs1468198
| AERD | 22 (15.6%) | 68 (48.2%) | 51 (36.2%) | 141 (100%) | 0.60 [0.47–0.78] | 9.53 × 10−4
| 0.001 | 0.47 [0.29–0.75] | 0.002 | 0.016 | 0.53 [0.37–0.78] | 0.001 | 0.010 |
ATA | 279 (28.1%) | 483 (48.7%) | 230 (23.2%) | 992 (100%) | ||||||||||
rs2074261
| AERD | 22 (15.6%) | 63 (44.7%) | 56 (39.7%) | 141 (100%) | 0.62 [0.48–0.8] | 2.30 × 10−4
| 0.002 | 0.54 [0.38–0.78] | 0.001 | 0.010 | 0.51 [0.31–0.82] | 0.005 | 0.048 |
ATA | 263 (26.5%) | 469 (47.2%) | 262 (26.4%) | 994 (100%) | ||||||||||
rs13301
| AERD | 22 (15.6%) | 65 (46.1%) | 54 (38.3%) | 141 (100%) | 0.64 [0.5–0.82] | 4.20 × 10−4
| 0.004 | 0.57 [0.39–0.83] | 0.003 | 0.027 | 0.5 [0.31–0.81] | 0.005 | 0.043 |
ATA | 265 (26.7%) | 468 (47.1%) | 261 (26.3%) | 994 (100%) | ||||||||||
Haplotype | ||||||||||||||
+/+ | −/+ | −/− | Total | |||||||||||
BL1ht1
| AERD | 16 (11.3%) | 57 (40.4%) | 68 (48.2%) | 141 (100%) | 0.78 [0.6–1.03] | 0.084 | 0.672 | 0.67 [0.47–0.96] | 0.028 | 0.226 | 0.94 [0.54–1.64] | 0.829 | 1.000 |
ATA | 119 (12.0%) | 498 (50.2%) | 376 (37.9%) | 993 (100%) | ||||||||||
BL1ht3
| AERD | 9 (6.4%) | 44 (31.2%) | 88 (62.4%) | 141 (100%) | 0.86 [0.64–1.17] | 0.343 | 1.000 | 0.79 [0.55–1.14] | 0.213 | 1.000 | 1.06 [0.51–2.21] | 0.873 | 1.000 |
ATA | 57 (5.7%) | 367 (37.0%) | 569 (57.3%) | 993 (100%) | ||||||||||
BL1ht4
| AERD | 0 (0.0%) | 9 (6.4%) | 132 (93.6%) | 141 (100%) | 0.86 [0.42–1.76] | 0.688 | 1.000 | 0.87 [0.42–1.79] | 0.709 | 1.000 | inf | 0.999 | 1.000 |
ATA | 1 (0.1%) | 71 (7.2%) | 921 (92.7%) | 993 (100%) | ||||||||||
BL2ht3
| AERD | 3 (2.1%) | 32 (22.7%) | 106 (75.2%) | 141 (100%) | 0.9 [0.62–1.3] | 0.565 | 1.000 | 0.86 [0.57–1.3] | 0.486 | 1.000 | 1.12 [0.33–3.85] | 0.856 | 1.000 |
ATA | 19 (1.9%) | 253 (25.4%) | 723 (72.7%) | 995 (100%) | ||||||||||
BL2ht4
| AERD | 0 (0%) | 6 (4.3%) | 135 (95.7%) | 141 (100%) | 0.77 [0.33–1.8] | 0.541 | 1.000 | 0.77 [0.33–1.84] | 0.560 | 1.000 | inf | 0.999 | 1.000 |
ATA | 1 (0.1%) | 54 (5.4%) | 940 (94.5%) | 995 (100%) |
Locus | Genotype | Codominant | Dominant | Recessive | |||||
---|---|---|---|---|---|---|---|---|---|
RR | CR | CC | P*
| Pcorr
**
| P*
| Pcorr
**
| P*
| Pcorr
**
| |
rs2074267
| 6.95 ± 0.76 (173) | 6.29 ± 0.46 (578) | 7.18 ± 0.59 (385) | 0.413 | 1.000 | 0.207 | 1.000 | 0.907 | 1.000 |
rs4141356
| 7.53 ± 0.90 (171) | 6.57 ± 0.48 (537) | 6.51 ± 0.51 (428) | 0.271 | 1.000 | 0.484 | 1.000 | 0.238 | 1.000 |
rs718100
| 8.27 ± 1.04 (146) | 6.36 ± 0.49 (513) | 6.56 ± 0.48 (477) | 0.138 | 1.000 | 0.500 | 1.000 | 0.043 | 0.391 |
rs2074265
| 8.15 ± 1.02 (149) | 6.46 ± 0.49 (516) | 6.48 ± 0.48 (471) | 0.120 | 1.000 | 0.389 | 1.000 | 0.058 | 0.535 |
rs2240299
| 4.99 ± 0.61 (138) | 6.33 ± 0.49 (492) | 7.51 ± 0.53 (505) | 0.006 | 0.053 | 0.015 | 0.139 | 0.041 | 0.376 |
rs7507755
| 4.99 ± 0.61 (138) | 6.33 ± 0.49 (492) | 7.50 ± 0.53 (506) | 0.006 | 0.055 | 0.016 | 0.145 | 0.041 | 0.379 |
rs1468198
| 5.67 ± 0.54 (301) | 6.59 ± 0.47 (551) | 8.02 ± 0.76 (281) | 0.004 | 0.033 | 0.008 | 0.072 | 0.033 | 0.307 |
rs2074261
| 5.76 ± 0.57 (285) | 6.47 ± 0.46 (532) | 7.88 ± 0.71 (318) | 0.006 | 0.057 | 0.009 | 0.078 | 0.061 | 0.560 |
rs13301
| 5.78 ± 0.57 (287) | 6.62 ± 0.47 (533) | 7.63 ± 0.69 (315) | 0.015 | 0.139 | 0.032 | 0.291 | 0.064 | 0.590 |
Haplotype | |||||||||
+/+ | −/+ | −/− | |||||||
BL1ht1
| 7.25 ± 0.55 (444) | 6.22 ± 0.46 (555) | 6.78 ± 0.82 (135) | 0.276 | 1.000 | 0.151 | 1.000 | 0.949 | 1.000 |
BL1ht3
| 6.89 ± 0.44 (657) | 6.22 ± 0.52 (411) | 7.58 ± 1.51 (66) | 0.693 | 1.000 | 0.563 | 1.000 | 0.845 | 1.000 |
BL1ht4
| 6.66 ± 0.34 (1053) | 7.16 ± 1.24 (80) | 3.00 (1) | 0.964 | 1.000 | 0.943 | 1.000 | 0.827 | 1.000 |
BL2ht3
| 6.70 ± 0.38 (829) | 6.65 ± 0.67 (285) | 6.91 ± 1.77 (22) | 0.818 | 1.000 | 0.752 | 1.000 | 0.845 | 1.000 |
BL2ht4
| 6.72 ± 0.34 (1075) | 6.21 ± 1.39 (60) | 0.00 (1) | 0.564 | 1.000 | 0.612 | 1.000 | 0.524 | 1.000 |
Association analysis using rs1468198 as a covariate
The risk of AERD | |||
SNP | OR [95% CI] | P*
| Pcorr
†
|
rs13301
| 1.16 [0.55–2.41] | 0.699 | 1.000 |
rs2074261
| 0.99 [0.47–2.09] | 0.975 | 1.000 |
rs7507755
| 0.78 [0.52–1.17] | 0.226 | 1.000 |
rs2240299
| 0.78 [0.52–1.16] | 0.220 | 1.000 |
rs2074265
| 1.24 [0.94–1.61] | 0.123 | 1.000 |
rs718100
| 1.24 [0.95–1.63] | 0.109 | 1.000 |
rs4141356
| 1.18 [0.91–1.53] | 0.222 | 1.000 |
rs2074267
| 0.96 [0.72–1.28] | 0.772 | 1.000 |
% decline of FEV1 | |||
SNP | β (± SE) | P**
| Pcorr
†
|
rs13301
| 1.08 ± 1.25 | 0.387 | 1.000 |
rs2074261
| 0.06 ± 1.29 | 0.964 | 1.000 |
rs7507755
| −0.64 ± 0.69 | 0.353 | 1.000 |
rs2240299
| −0.65 ± 0.69 | 0.344 | 1.000 |
rs2074265
| 0.34 ± 0.51 | 0.505 | 1.000 |
rs718100
| 0.31 ± 0.51 | 0.535 | 1.000 |
rs4141356
| 0.19 ± 0.49 | 0.702 | 1.000 |
rs2074267
| 0.12 ± 0.52 | 0.814 | 1.000 |