Introduction
Materials and methods
Study population
Study variables
IL13 genotyping
SNPs | Position (bp) | Location | Genotype | Frequency (%) |
---|---|---|---|---|
rs1800925 | 132,020,708 | Promoter | CC | 577 (63.6) |
(-1112C/T) | CT | 295 (32.5) | ||
TT | 35 (3.9) | |||
Total | 907 (100.0) | |||
rs2066960 | 132,022,334 | Intron 1 | CC | 729 (81.5) |
AC | 157 (17.6) | |||
AA | 8 (0.9) | |||
Total | 894 (100.0) | |||
rs1295686 | 132,023,742 | Intron 3 | CC | 483 (64.6) |
CT | 240 (32.1) | |||
TT | 25 (3.3) | |||
Total | 748 (100.0) | |||
rs20541 | 132,023,863 | Exon 4 | GG | 583 (64.4) |
(R130Q) | GA | 291 (32.1) | ||
AA | 32 (3.5) | |||
Total | 906 (100.0) | |||
rs1295685 | 132,024,344 | Exon 4 | GG | 584 (64.5) |
GA | 280 (30.9) | |||
AA | 41 (4.5) | |||
Total | 905 (100.0) |
Birth order
Skin Prick Testing (SPT)
Serum Total IgE Determination
Maternal Atopic Status
Serum Specific Inhalant IgE Screening
Family Social Status Cluster
Environmental Tobacco Smoke Exposure
Data analysis and statistics
Results
Participant demographic characteristics
IgE at age 10 (n (%)) | No IgE at age 10 (n (%)) | Exact | |
---|---|---|---|
Study Variables
|
N = 953
|
N = 583
|
p-values
|
Birth order | |||
- First | 354 (41.0) | 156 (44.7) | 0.50 |
- Second | 303 (35.1) | 116 (33.2) | |
- Third or higher | 206 (23.9) | 77 (22.1) | |
Family Social Status Cluster* | |||
- High | 80 (8.5) | 31 (7.5) |
0.02
|
- Middle | 737 (78.0) | 300 (72.8) | |
- Low | 128 (13.5) | 81 (19.7) | |
Environmental Tobacco Exposure** | |||
- ETS-0 | 451 (47.5) | 196 (36.0) |
<0.0001
|
- ETS-1 | 300 (31.6) | 164 (30.1) | |
- ETS-2 | 199 (21.0) | 185 (33.9) | |
Gender | |||
- Male | 479 (50.3) | 306 (52.7) | 0.37 |
- Female | 474 (49.7) | 275 (47.3) | |
Prematurity (weeks) | |||
- < 37 | 26 (2.8) | 23 (4.1) | 0.23 |
- ≥ 37 | 904 (97.2) | 544 (95.9) | |
Low Birth Weight (g) | |||
- < 2500 | 33 (3.6) | 28 (4.9) | 0.23 |
- ≥ 2500 | 894 (96.4) | 539 (95.1) |
Association of birth order and IL13 polymorphisms with total serum IgE and inhalant IgE screen at age 10, and with skin prick test positivity at ages 4, 10 and 18 years
Univariable analysis
Elevated serum IgE (age 10)
|
Inhalant IgE +ve (age 10)
| |||
---|---|---|---|---|
n (%)
|
Exact
|
n (%)
|
Exact
| |
Study Variables
|
N = 953
|
p-values
|
N = 952
|
p-values
|
rs1800925: | ||||
- TT/CT | 108 (33.0) | 0.086 | 117 (35.9) | 0.191 |
- CC | 173 (27.6) | 197 (31.5) | ||
rs2066960: | ||||
- AA/AC | 62 (38.0) |
0.011
| 58 (35.8) | 0.410 |
- CC | 219 (27.7) | 256 (32.4) | ||
rs20541: | ||||
- AA/GA | 104 (32.6) | 0.153 | 114 (35.9) | 0.189 |
- GG | 177 (27.9) | 200 (31.6) | ||
Birth order | ||||
- First | 98 (27.7) | 0.659 | 116 (32.8) | 0.683 |
- Second | 91 (30.0) | 105 (34.8) | ||
- Third or higher | 64 (31.1) | 64 (31.1) | ||
- Latent | 33 (47.8) | 31 (44.9) | ||
Family Social Status Cluster* | ||||
- High | 22 (27.5) | 0.328 | 22 (27.5) | 0.363 |
- Middle | 213 (28.9) | 251 (34.1) | ||
- Low | 45 (35.2) | 38 (29.7) | ||
Environmental Tobacco Exposure** | ||||
- ETS-0 | 142 (31.5) | 0.463 | 160 (35.6) | 0.237 |
- ETS-1 | 85 (28.3) | 89 (29.7) | ||
- ETS-2 | 54 (27.1) | 64 (32.2) | ||
Gender | ||||
- Male | 146 (30.5) | 0.523 | 178 (37.2) |
0.006
|
- Female | 135 (28.5) | 136 (28.7) | ||
Prematurity (weeks) | ||||
- < 37 | 14 (53.9) |
0.008
| 14 (53.9) |
0.032
|
- ≥ 37 | 257 (28.4) | 290 (32.1) | ||
Low Birth Weight (g) | ||||
- < 2500 | 8 (24.2) | 0.566 | 11 (33.3) | 1.000 |
- ≥ 2500 | 265 (29.6) | 291 (32.6) | ||
Maternal History of Atopy | ||||
- Yes | 100 (30.7) | 0.600 | 125 (38.3) |
0.013
|
- No | 181 (28.9) | 189 (30.2) | ||
Maternal IgE | ||||
- > 100 | 65 (37.4) | 0.009 | 73 (42.0) |
0.002
|
- ≤ 100 | 130 (26.7) | 140 (28.8) | ||
Maternal Atopic Status*** | ||||
- Definite | 32 (30.5) | 0.006 | 42 (40.0) |
0.014
|
- Latent | 33 (47.8) | 31 (45.0) | ||
- Probable | 31 (26.3) | 35 (30.0) | ||
- None | 99 (26.8) | 105 (28.5) | ||
Cord Serum IgE | ||||
- ≥ 0.5 | 34 (43.6) | 0.004 | 37 (47.4) |
0.005
|
- < 0.5 | 202 (27.4) | 229 (31.0) |
Positive SPT (age 4)
|
Positive SPT (age 10)
|
Positive SPT (age 18)
| ||||
---|---|---|---|---|---|---|
n (%)
|
Exact
|
n (%)
|
Exact
|
n (%)
|
Exact
| |
Study Variables
|
N = 981
|
p-values
|
N = 1,036
|
p-values
|
N = 845
|
p-values
|
rs1800925: | ||||||
- TT/CT | 56 (21.8) | 0.317 | 94 (28.7) | 0.365 | 105 (43.6) | 0.354 |
- CC | 137 (18.9) | 183 (25.9) | 242 (40.1) | |||
rs2066960: | ||||||
- AA/AC | 31 (23.9) | 0.195 | 50 (30.7) | 0.247 | 47 (39.8) | 0.840 |
- CC | 162 (19.0) | 227 (26.0) | 300 (41.3) | |||
rs20541: | ||||||
- AA/GA | 54 (20.9) | 0.584 | 89 (27.6) | 0.705 | 98 (42.1) | 0.754 |
- GG | 139 (19.2) | 188 (26.3) | 249 (40.7) | |||
Birth order | ||||||
- First | 84 (21.1) | 0.549 | 107 (27.2) | 0.950 | 130 (39.5) | 0.121 |
- Second | 67 (19.6) | 89 (27.6) | 116 (47.4) | |||
- Third or higher | 42 (17.5) | 57 (26.4) | 73 (39.3) | |||
Family Social Status Cluster* | ||||||
- High | 20 (23.8) | 0.492 | 19 (22.9) | 0.516 | 25 (36.8) |
0.023
|
- Middle | 150 (19.7) | 221 (27.7) | 276 (43.1) | |||
- Low | 23 (17.2) | 35 (24.3) | 33 (29.7) | |||
Environmental Tobacco Exposure** | ||||||
- ETS-0 | 100 (21.9) | 0.145 | 141 (28.9) | 0.213 | 183 (43.8) | 0.245 |
- ETS-1 | 63 (19.4) | 86 (26.2) | 97 (38.5) | |||
- ETS-2 | 30 (15.2) | 49 (22.6) | 63 (37.5) | |||
Gender | ||||||
- Male | 109 (22.1) | 0.055 | 158 (30.6) |
0.005
| 188 (46.2) |
0.002
|
- Female | 84 (17.2) | 119 (22.9) | 156 (35.7) | |||
Prematurity (weeks) | ||||||
- < 37 | 5 (17.2) | 1.000 | 12 (41.4) | 0.086 | 9 (39.1) | 1.000 |
- ≥ 37 | 183 (19.7) | 257 (26.2) | 321 (40.4) | |||
Low Birth Weight (g) | ||||||
- < 2500 | 4 (11.1) | 0.283 | 11 (31.4) | 0.559 | 9 (34.6) | 0.685 |
- ≥ 2500 | 184 (20.0) | 256 (26.3) | 321 (40.7) | |||
Maternal History of Atopy | ||||||
- Yes | 75 (22.1) | 0.178 | 117 (32.7) | 0.002 | 137 (47.6) |
0.005
|
- No | 118 (18.4) | 160 (23.6) | 207 (37.4) | |||
Maternal IgE | ||||||
- > 100 | 40 (22.4) | 0.223 | 68 (34.3) | 0.002 | 78 (48.8) |
0.002
|
- ≤ 100 | 90 (18.0) | 116 (22.4) | 146 (34.5) | |||
Maternal Atopic Status*** | ||||||
- Definite | 20 (19.2) | 0.355 | 40 (33.9) | 0.010 | 48 (49.5) |
0.008
|
- Latent | 20 (26.7) | 28 (35.0) | 30 (47.6) | |||
- Probable | 24 (18.8) | 32 (25.0) | 42 (40.0) | |||
- None | 66 (17.7) | 84 (21.5) | 104 (32.7) | |||
Cord Serum IgE | ||||||
- ≥ 0.5 | 29 (32.2) | 0.002 | 32 (35.6) | 0.042 | 37 (50.0) | 0.060 |
- < 0.5 | 134 (17.8) | 201 (25.2) | 253 (38.4) |
Multivariable analysis
Elevated serum IgE at age 10 years
Serum specific inhalant IgE screen positivity at age 10 years
1st Born | 2nd Born | 3rd and Higher | ||||
---|---|---|---|---|---|---|
Study Variables
|
p
|
PR (95% CI)
|
p
|
PR (95% CI)
|
p
|
PR (95% CI)
|
n = 246 | n = 212 | n = 130 | ||||
rs1800925: | ||||||
-TT/CT vs. CC |
0.007
| 1.73 (1.16, 2.57) | 0.165 | 0.72 (0.45, 1.15) | 0.794 | 0.93 (0.54, 1.61) |
Gender (M vs. F) | 0.499 | 1.14 (0.77, 1.71) | 0.208 | 1.31 (0.86, 1.99) | 0.350 | 1.28 (0.76, 2.15) |
Smoke exposure*: | ||||||
- ETS-1 vs. ETS-0 | 0.38 | 0.82 (0.53, 1.27) | 0.175 | 0.70 (0.42, 1.17) | 0.863 | 0.95 (0.54, 1.69) |
- ETS-2 vs. ETS-0 | 0.064 | 0.54 (0.28, 1.04) | 0.202 | 0.65 (0.33, 1.26) | 0.536 | 0.79 (0.38, 1.66) |
Family SES Cluster**: | ||||||
- Low vs. High | 0.198 | 1.88 (0.72, 4.91) | 0.840 | 1.09 (0.49, 2.40) | 0.589 | 0.72 (0.21, 2.41) |
- Middle vs. High | 0.767 | 1.13 (0.50, 2.54) | 0.379 | 0.76 (0.41, 1.41) | 0.915 | 1.05 (0.43, 2.54) |
Gestational Age | 0.173 | 0.93 (0.83, 1.03) | 0.246 | 1.09 (0.94, 1.28) | 0.582 | 1.06 (0.86, 1.31) |
1st Born | 2nd Born | 3rd and Higher | ||||
---|---|---|---|---|---|---|
Study Variables
|
p
|
PR (95% CI)
|
p
|
PR (95% CI)
|
p
|
PR (95% CI)
|
n = 246 | n = 212 | n = 130 | ||||
rs20541: | ||||||
-AA/GA vs. GG |
0.034
| 1.48 (1.03, 2.13) | 0.120 | 0.72 (0.48, 1.09) | 0.197 | 1.43 (0.83, 2.45) |
Gender (M vs. F) | 0.353 | 1.19 (0.82, 1.72) |
0.017
| 1.58 (1.08, 2.29) | 0.496 | 1.20 (0.71, 2.02) |
Smoke Exposure*: | ||||||
- ETS-1 vs. ETS-0 | 0.075 | 0.68 (0.44, 1.04) | 0.154 | 0.73 (0.47, 1.13) | 0.600 | 0.84 (0.45, 1.60) |
- ETS-2 vs. ETS-0 | 0.318 | 0.79 (0.49, 1.26) | 0.278 | 0.74 (0.43, 1.27) | 0.672 | 1.14 (0.60, 2.19) |
Family SES Cluster** | ||||||
- Low vs. High | 0.070 | 2.27 (0.94, 5.49) | 0.860 | 0.92 (0.35, 2.43) | 0.058 | 0.23 (0.05, 1.05) |
- Middle vs. High | 0.435 | 1.37 (0.62, 3.04) | 0.506 | 1.26 (0.64, 2.46) | 0.349 | 0.69 (0.31, 1.51) |
Gestational age | 0.240 | 0.94 (0.85, 1.04) | 0.649 | 1.03 (0.90, 1.18) | 0.095 | 1.26 (0.96, 1.65) |
Skin prick tests at 4, 10 and 18 years: Cross-sectional analyses
Skin prick tests at 4, 10 and 18 years: Repeatedmeasurement analysis
1st Born | 2nd Born | 3rd and Higher | ||||
---|---|---|---|---|---|---|
Study Variables
|
p
|
PR (95% CI)
|
p
|
PR (95% CI)
|
p
|
PR (95% CI)
|
(n = 354; obs = 772)# | (n = 287; obs = 634) | (n = 184; obs = 414) | ||||
rs20541: | ||||||
-AA/GA vs. GG |
0.007
| 1.35 (1.09, 1.69) | 0.045 | 0.75 (0.56, 0.99) | 0.075 | 1.35 (0.97, 1.89) |
Gender (M vs. F) |
0.014
| 1.32 (1.06, 1.66) |
0.001
| 1.50 (1.18, 1.89) | 0.082 | 1.34 (0.96, 1.85) |
Environmental Smoke Exposure*: | ||||||
- ETS-1 vs. ETS-0 | 0.577 | 0.93 (0.73, 1.19) | 0.698 | 1.05 (0.81, 1.36) | 0.179 | 0.76 (0.52, 1.13) |
- ETS-2 vs. ETS-0 |
0.020
| 0.65 (0.45, 0.93) | 0.101 | 0.75 (0.53, 1.06) | 0.309 | 0.79 (0.50, 1.25) |
Family SES Cluster**: | ||||||
- Low vs. High | 0.099 | 1.51 (0.93, 2.45) | 0.331 | 0.73 (0.39, 1.38) |
0.006
| 0.34 (0.16, 1.37) |
- Middle vs. High | 0.741 | 1.07 (0.70, 1.64) | 0.355 | 1.24 (0.78, 1.97) | 0.091 | 0.67 (0.43, 1.06) |
Gestational Age | 0.377 | 0.96 (0.89, 1.04) |
0.033
| 1.10 (1.01, 1.21) |
0.010
| 1.24 (1.05, 1.47) |