Background
Methods
Study subjects
Selection of polymorphisms in the human TSLP gene
Single nucleotide polymorphism genotyping
Statistical analyses
Results
Population characteristics
Demographic index | AR (n = 368) | Controls (n = 325) |
---|---|---|
Age Mean (Range) (years) | 27.08 ± 0.77 (18–71) | 36.22 ± 0.84 (18–78) |
Sex, Male/Female, No. (%) | 227 (60.1) /151 (39.9) | 175 (53.0) / 155 (47.0) |
Total IgE Mean (Range), kU/l | 325.35 ± 31.70 (6.9-5000) | 69.14 ± 9.35 (2–906) |
Individual SNP association analysis
Gene: locus and OMIMNo.a
| No. | SNP_ID | Chromosome Positionb
| Intermarker distances (bp) | Genic location | Base Change | MAFc
| Pf
| P value for HWEgtest | ||
---|---|---|---|---|---|---|---|---|---|---|---|
NCBId
| Casee
| Control | |||||||||
1 | rs1545169 | 110427275 | —— | 5′ near gene | T/G | 0.476 | 0.292 | 0.278 | 0.6928 |
<0.0000
| |
2 | rs764917 | 110428406 | 1131 | 5′ near gene | A/C | 0.205 | 0.284 | 0.289 | 0.5036 |
0.0004
| |
3 | rs12653736 | 110428526 | 120 | 5′ near gene | G/T | 0.062 | 0.104 | 0.113 | 0.8689 | 0.6270 | |
4 | rs1837253 | 110429771 | 1245 | 5′ near gene | T/C | 0.389 | 0.467 | 0.460 | 0.5430 | 0.7337 | |
5 | rs12654933 | 110430654 | 883 | 5′ near gene | C/A | 0.244 | 0.154 | 0.144 | 0.7575 | 0.8902 | |
6 | rs10455025 | 110432898 | 2244 | 5′ near gene | A/C | 0.067 | 0.050 | 0.048 | 0.9790 | 0.3650 | |
TSLP: 5q22.1 | 7 | rs11466741 | 110436604 | 3706 | Intron 2 | C/T | 0.211 | 0.313 | 0.329 | 0.8127 | 0.2428 |
8 | rs13156086 | 110443368 | 6764 | 3′ near gene | A/C | 0.144 | 0.239 | 0.251 | 0.6890 | 0.7148 | |
9 | rs6886755 | 110443500 | 132 | 3′ near gene | G/T | 0.089 | 0.077 | 0.073 | 0.9559 | 0.5559 | |
10 | rs252706 | 110444759 | 1259 | 3′ near gene | G/A | 0.337 | 0.327 | 0.337 | 0.8165 | 0.0635 | |
11 | rs2416259 | 110447641 | 2882 | 3′ near gene | T/C | 0.411 | 0.369 | 0.366 | 0.6565 | 0.1416 |
SNP ID | Genotype | AR subjects | Control subjects | P (2 df)a
| Logistic regression | |||
---|---|---|---|---|---|---|---|---|
No. | Frequency | No. | Frequency | OR (95%CI) | Pb
| |||
rs12653736 | GG | 290 | 79.89% | 255 | 78.95% | 0.852 | 1.00 (referent) | |
GT | 66 | 18.18% | 63 | 19.50% | 0.999 (0.667-1.496) | 0.996 | ||
TT | 7 | 1.93% | 5 | 1.55% | 1.073 (0.322-3.572) | 0.909 | ||
rs1837253 | TT | 98 | 26.85% | 90 | 28.66% | 0.828 | 1.00 (referent) | |
TC | 186 | 50.96% | 159 | 50.64% | 1.043 (0.719-1.514) | 0.823 | ||
CC | 81 | 22.19% | 65 | 20.70% | 1.078 (0.686-1.696) | 0.744 | ||
rs12654933 | CC | 269 | 73.30% | 237 | 73.37% | 0.659 | 1.00 (referent) | |
CA | 86 | 23.43% | 79 | 24.46% | 1.012 (0.701-1.463) | 0.948 | ||
AA | 12 | 3.27% | 7 | 2.17% | 1.151 (0.429-3.092) | 0.780 | ||
rs10455025 | AA | 333 | 90.74% | 292 | 90.40% | 0.622 | 1.00 (referent) | |
AC | 33 | 8.99% | 31 | 9.60% | 0.867 (0.503-1.492) | 0.605 | ||
CC | 1 | 0.27% | 0 | 0.00% | NAc
| NAc
| ||
rs11466741 | CC | 134 | 46.69% | 112 | 46.67% | 0.879 | 1.00 (referent) | |
CT | 121 | 42.16% | 98 | 40.83% | 0.993 (0.675-1.461) | 0.972 | ||
TT | 32 | 11.15% | 30 | 12.50% | 0.816 (0.454-1.469) | 0.498 | ||
rs13156086 | AA | 198 | 58.24% | 169 | 56.52% | 0.909 | 1.00 (referent) | |
AC | 120 | 35.29% | 110 | 36.79% | 0.903 (0.639-1.277) | 0.564 | ||
CC | 22 | 6.47% | 20 | 6.69% | 0.826 (0.423-1.613) | 0.576 | ||
rs6886755 | GG | 317 | 86.38% | 276 | 85.71% | 0.624 | 1.00 (referent) | |
GT | 47 | 12.81% | 45 | 13.98% | 0.793 (0.501-1.256) | 0.323 | ||
TT | 3 | 0.82% | 1 | 0.31% | 2.535 (0.255-25.235) | 0.428 | ||
rs252706 | GG | 163 | 44.54% | 149 | 46.27% | 0.831 | 1.00 (referent) | |
GA | 155 | 42.35% | 129 | 40.06% | 1.174 (0.837-1.646) | 0.353 | ||
AA | 48 | 13.11% | 44 | 13.66% | 1.120 (0.684-1.832) | 0.653 | ||
rs2416259 | TT | 139 | 38.08% | 126 | 42.14% | 0.335 | 1.00 (referent) | |
TC | 176 | 48.22% | 127 | 42.47% | 1.361 (0.960-1.928) | 0.083 | ||
CC | 50 | 13.70% | 46 | 15.38% | 1.122 (0.689-1.828) | 0.644 |
LD Analysis and Haplotype Block Structure
Haplotype analysis
Block | AR subjects | Control subjects | Pa
| Psim
b
| Hap. Scorec
| Logistic regression | Global score testf
| |||
---|---|---|---|---|---|---|---|---|---|---|
No. | Frequency | No. | Frequency | OR (95% CI) | Pd
| |||||
Block1: rs12654933-rs11466741-rs13156086 | ||||||||||
CCA | 382 | 52.10% | 339 | 52.30% | 0.9211 | 0.6622 | 0.44067 | 1.00 (referent) | Global-stat = 0.49867, df = 4, p-val = 0.97363, Psim
b = 0.97596 | |
CTC | 180.3 | 24.60% | 165.1 | 25.50% | 0.6940 | 0.5274 | −0.63567 | 0.933 (0.716-1.217) | 0.610 | |
ACA | 109 | 14.90% | 91.5 | 14.10% | 0.7014 | 0.80357 | 0.25053 | 1.029 (0.743-1.426) | 0.863 | |
CTA | 56.5 | 7.70% | 48.4 | 7.50% | 0.8739 | 0.83692 | −0.20715 | 1.002 (0.604-1.664) | 0.993 | |
Others | 5.1 | 0.70% | 3.9 | 0.60% | NAe
| NAe
| NAe
| NAe
| NAe
| |
Block2: rs6886755-rs252706 | ||||||||||
GG | 430.8 | 58.50% | 383.1 | 58.90% | 0.8761 | 0.70783 | −0.37559 | 1.00 (referent) | Global-stat = 0.71243, df = 2, p-val = 0.70032, Psim
b = 0.70097 | |
GA | 252.1 | 34.30% | 219.2 | 33.70% | 0.8355 | 0.4783 | 0.70725 | 1.073 (0.845-1.362) | 0.563 | |
TG | 53.1 | 7.20% | 47.7 | 7.30% | 0.9336 | 0.55034 | −0.60092 | 0.913 (0.592-1.408) | 0.681 |
Block | 0-copy | 1-copy logistic regression | 2-copy logistic regression | P (2 df)b
| |||||
---|---|---|---|---|---|---|---|---|---|
AR/C | OR (95%CI) | AR/C | Pa
| OR (95%CI) | AR/C | Pa
| OR (95%CI) | ||
Block1: rs12654933-rs11466741-rs13156086 | |||||||||
CCA | 85/75 | 1.000 (referent) | 167/144 | 0.583 | 1.118 (0.750-1.667) | 116/106 | 0.770 | 1.066 (0.695-1.633) | 0.947 |
CTA | 332/294 | 1.000 (referent) | 33/30 | 0.709 | 0.902 (0.526-1.548) | 3/1 | 0.414 | 2.606 (0.262-25.927) | 0.676 |
CTC | 208/178 | 1.000 (referent) | 136/126 | 0.561 | 0.907 (0.653-1.260) | 24/21 | 0.739 | 0.896 (0.468-1.713) | 0.884 |
ACA | 270/240 | 1.000 (referent) | 86/78 | 0.869 | 1.031 (0.714-1.491) | 12/7 | 0.763 | 1.164 (0.434-3.125) | 0.668 |
Block2: rs6886755-rs252706 | |||||||||
GG | 67/60 | 1.000 (referent) | 171/147 | 0.888 | 1.032 (0.667-1.595) | 130/118 | 0.796 | 0.942 (0.600-1.480) | 0.946 |
GA | 164/149 | 1.000 (referent) | 156/132 | 0.436 | 1.143 (0.817-1.600) | 48/44 | 0.678 | 1.110 (0.679-1.815) | 0.893 |
TG | 318/279 | 1.000 (referent) | 47/45 | 0.342 | 0.800 (0.505-1.267) | 3/1 | 0.423 | 2.558 (0.257-25.465) | 0.629 |