Background
Methods
Subjects
Determination of sample size
Study procedures
Blood samples and DNA isolation
Genotyping
Statistical analysis
Results
Demographic data of the participants
Characteristics
|
TB (
n
= 109) No. (%)
|
LTBI (
n
= 225) No. (%)
|
HC (
n
= 422) No. (%)
|
χ
2
/ANOVA TB.vs.LTBI
|
χ
2
/ANOVA LTBI.vs.HC
|
---|---|---|---|---|---|
Age, mean ± SD, (yrs) | 45 ± 12.6 | 45 ± 16.5 | 45 ± 18.7 | 0.99 | 0.96 |
15~ | 16(14.7) | 34(15.1) | 63(14.9) | 1.00 | 1.00 |
30~ | 27(24.8) | 56(24.9) | 105(24.9) | ||
45~ | 45(41.2) | 92(40.9) | 173(41.0)) | ||
60~ | 21(19.3) | 43(19.1) | 81(19.2) | ||
Male | 74(67.9) | 152(67.6) | 285(67.5) | 0.951 | 1.000 |
BCG vaccination | 95(87.2) | 214(95.1) | 405(96.0) | 0.01a | 0.99 |
SNP analysis
dbSNPS
|
Genotypes
|
Frequencies (No., %)
|
LTBI.vs.HC
|
TB.vs.LTBI
|
TB.vs.HC
| ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HC (
n
= 422)
|
LTBI (
n
= 225)
|
TB (
n
= 109)
|
p
|
OR
|
95% CI
|
p
|
OR
|
95% CI
|
p
|
OR
|
95% CI
| ||
rs5743618 | GG | 2(0.5) | 2(0.9) | 1(0.9) | 0.613 | 1.883 | 0.264-13.461 | 0.979 | 1.032 | 0.093-11.511 | 0.499 | 1.944 | 0.175-21.64 |
TG | 70(16.6) | 23(10.2) | 10(9.2) | 0.028 | 0.573 | 0.347-0.946 | 0.763 | 0.887 | 0.407-1.936 | 0.054 | 0.508 | 0.252-1.022 | |
TT | 350(82.9) | 200(88.9) | 98(89.9) | 0.043 | 1.646 | 1.011-2.678 | 0.778 | 1.114 | 0.526-2.356 | 0.074 | 1.833 | 0.935-3.592 | |
rs3804099 | CC | 51(12.1) | 25(11.1) | 9(8.3) | 0.714 | 0.909 | 0.547-1.512 | 0.419 | 0.720 | 0.324-1.600 | 0.260 | 0.655 | 0.312-1.375 |
TC | 180(42.6) | 95(42.2) | 36(33.0) | 0.916 | 0.982 | 0.708-1.363 | 0.107 | 0.675 | 0.418-1.089 | 0.068 | 0.663 | 0.426-1.033 | |
TT | 191(45.3) | 105(46.7) | 64(58.7) | 0.732 | 1.058 | 0.765-1.464 | 0.039 | 1.625 | 1.023-2.581 | 0.012 | 1.720 | 1.123-2.636 | |
rs5743708 | GA | 4(0.9) | 9(4.0) | 6(5.5) | 0.008 | 4.354 | 1.326-14.301 | 0.534 | 1.398 | 0.485-4.033 | 0.002 | 6.087 | 1.687-21.968a |
GG | 418(99.1) | 216(96.0) | 103(94.5) | 0.008 | 0.229 | 0.051-0.836 | 0.534 | 0.715 | 0.221-2.513 | 0.002 | 0.164 | 0.046-0.593a | |
rs3804100 | CC | 42(10.0) | 45(20.0) | 21(19.2) | <0.001 | 2.262 | 1.433-3.570a | 0.875 | 0.955 | 0.536-1.700 | 0.007 | 2.159 | 1.218-3.829 |
TC | 168(39.8) | 90(40.0) | 44(40.4) | 0.963 | 1.008 | 0.724-1.402 | 0.949 | 1.015 | 0.637-1.619 | 0.916 | 1.023 | 0.666-1.572 | |
TT | 212(50.2) | 90(40.0) | 44(40.4) | 0.013 | 0.660 | 0.476-0.917 | 0.949 | 0.985 | 0.618-1.570 | 0.066 | 0.671 | 0.437-1.028 | |
rs1898830 | AA | 142(33.6) | 68(30.2) | 33(30.3) | 0.375 | 0.854 | 0.602-1.211 | 0.992 | 1.003 | 0.609-1.649 | 0.504 | 0.856 | 0.543-1.351 |
AG | 196(46.4) | 113(50.2) | 54(49.5) | 0.360 | 1.163 | 0.842-1.608 | 0.907 | 0.973 | 0.616-1.538 | 0.564 | 1.132 | 0.743-1.725 | |
GG | 84(20.0) | 44(19.6) | 22(20.2) | 0.915 | 0.978 | 0.651-1.469 | 0.893 | 1.040 | 0.587-1.843 | 0.948 | 1.018 | 0.602-1.720 | |
rs4986790 | AA | 346(82.0) | 181(80.4) | 77(70.6) | 0.630 | 0.904 | 0.598-1.365 | 0.045 | 0.585 | 0.345-0.991 | 0.009 | 0.529 | 0.327-0.855 |
AG | 75(17.8) | 42(18.7) | 31(28.4) | 0.778 | 1.062 | 0.699-1.613 | 0.043 | 1.732 | 1.094-3.050 | 0.013 | 1.839 | 1.132-2.987 | |
GG | 1(0.2) | 2(0.9) | 1(0.9) | 0.245 | 3.776 | 0.341-41.869 | 0.979 | 1.032 | 0.093-11.51 | 0.369 | 3.898 | 0.242-62.825 | |
rs4986791 | CC | 342(81.0) | 179(79.6) | 74(67.9) | 0.649 | 0.910 | 0.607-1.365 | 0.020 | 0.543 | 0.324-0.911 | 0.003 | 0.495 | 0.309-0.791 |
CT | 76(18.0) | 43(19.1) | 32(29.4) | 0.730 | 1.076 | 0.710-1.629 | 0.035 | 1.759 | 1.036-2.987 | 0.009 | 1.892 | 1.169-3.061 | |
TT | 4(1.0) | 3(1.3) | 3(2.7) | 0.699 | 1.412 | 0.313-6.365 | 0.396 | 2.094 | 0.416-10.551 | 0.141 | 2.958 | 0.652-13.415 | |
rs11536889 | CC | 34(8.1) | 17(7.6) | 10(9.2) | 0.822 | 0.933 | 0.509-1.701 | 0.611 | 1.236 | 0.546-2.798 | 0.706 | 1.153 | 0.551-2.413 |
GC | 167(39.5) | 86(38.2) | 40(36.7) | 0.737 | 0.945 | 0.678-1.317 | 0.787 | 0.937 | 0.584-1.504 | 0.583 | 0.885 | 0.573-1.368 | |
GG | 221(52.4) | 122(54.2) | 59(54.1) | 0.653 | 1.077 | 0.779-1.490 | 0.987 | 0.996 | 0.630-1.577 | 0.743 | 1.073 | 0.703-1.637 | |
rs10759932 | CC | 42(10.0) | 21(9.3) | 5(4.5) | 0.800 | 0.931 | 0.537-1.616 | 0.129 | 0.467 | 0.171-1.274 | 0.079 | 0.435 | 0.168-1.127 |
TC | 168(39.8) | 90(40.0) | 49(45.0) | 0.963 | 1.008 | 0.724-1.402 | 0.389 | 1.225 | 0.772-1.945 | 0.330 | 1.235 | 0.807-1.888 | |
TT | 212(50.2) | 114(50.7) | 55(50.5) | 0.917 | 1.017 | 0.736-1.406 | 0.972 | 0.992 | 0.628-1.567 | 0.967 | 1.009 | 0.662-1.537 | |
rs7873784 | CC | 29(6.9) | 19(8.4) | 7(6.4) | 0.467 | 1.250 | 0.684-2.283 | 0.518 | 0.744 | 0.303-1.827 | 0.868 | 0.930 | 0.396-2.184 |
GC | 135(32.0) | 57(25.4) | 18(16.5) | 0.078 | 0.721 | 0.501-1.037 | 0.070 | 0.583 | 0.324-1.050 | 0.001 | 0.421 | 0.244-0.726a | |
GG | 258(61.1) | 149(66.2) | 84(77.1) | 0.202 | 1.246 | 0.888-1.748 | 0.043 | 1.714 | 1.014-2.897 | 0.002 | 2.136 | 1.312-3.478a | |
rs10759931 | AA | 143(33.9) | 90(40.0) | 44(40.4) | 0.123 | 1.301 | 0.931-1.817 | 0.949 | 1.015 | 0.637-1.619 | 0.207 | 1.321 | 0.857-2.035 |
AG | 215(50.9) | 113(50.2) | 54(49.5) | 0.860 | 0.971 | 0.703-1.343 | 0.907 | 0.973 | 0.616-1.538 | 0.793 | 0.945 | 0.620-1.440 | |
GG | 64(15.2) | 22(9.8) | 11(10.1) | 0.055 | 0.606 | 0.363-1.014 | 0.928 | 1.036 | 0.483-2.221 | 0.175 | 0.628 | 0.319-1.236 | |
rs5743810 | CT | 12(2.8) | 8(3.6) | 5(4.6) | 0.618 | 1.260 | 0.507-3.128 | 0.648 | 1.304 | 0.416-4.084 | 0.357 | 1.643 | 0.566-4.766 |
TT | 410(97.2) | 217(96.4) | 104(95.4) | 0.618 | 0.790 | 0.293-2.276 | 0.648 | 0.773 | 0.215-3.057 | 0.357 | 0.609 | 0.210-1.766 | |
TLR8_129 | CC | 133(31.5) | 81(36.0) | 52(47.7) | 0.248 | 1.222 | 0.869-1.719 | 0.040 | 1.622 | 1.020-2.580 | 0.002 | 1.982 | 1.292-3.042a |
CG | 190(45.0) | 96(42.7) | 41(37.6) | 0.565 | 0.909 | 0.656-1.259 | 0.379 | 0.810 | 0.507-1.295 | 0.164 | 0.736 | 0.478-1.134 | |
GG | 99(23.5) | 48(21.3) | 16(14.7) | 0.539 | 0.885 | 0.599-1.307 | 0.147 | 0.634 | 0.342-1.178 | 0.047 | 0.561 | 0.315-0.999 | |
rs5743836 | CC | 25(5.9) | 13(5.8) | 6(5.5) | 0.940 | 0.974 | 0.488-1.943 | 0.919 | 0.950 | 0.351-2.571 | 0.868 | 0.925 | 0.370-2.314 |
TC | 181(42.9) | 125(55.5) | 49(45.0) | 0.002 | 1.664 | 1.201-2.306 | 0.069 | 0.653 | 0.412-1.035 | 0.698 | 1.087 | 0.712-1.661 | |
TT | 216(51.2) | 87(38.7) | 54(49.5) | 0.002 | 0.601 | 0.433-0.836 | 0.059 | 1.557 | 0.982-2.471 | 0.760 | 0.936 | 0.614-1.427 | |
rs1870884 | CC | 3(0.7) | 1(0.4) | 0(0) | 1.000 | 0.624 | 0.064-6.029 | - | |||||
TC | 107(25.4) | 56(24.9) | 27(24.8) | 0.896 | 0.976 | 0.672-1.417 | 0.981 | 0.994 | 0.585-1.687 | 0.900 | 0.969 | 0.596-1.578 | |
TT | 312(73.9) | 168(74.7) | 82(75.2) | 0.839 | 1.039 | 0.717-1.506 | 0.912 | 1.030 | 0.607-1.748 | 0.783 | 1.071 | 0.658-1.741 | |
TIRAP_975 | CC | 313(74.2) | 153(68.0) | 61(56.0) | 0.096 | 0.740 | 0.519-1.055 | 0.032 | 0.598 | 0.374-0.957 | <0.001 | 0.443 | 0.286-0.685a |
CT | 97(23.0) | 61(27.1) | 40(36.7) | 0.245 | 1.246 | 0.860-1.806 | 0.074 | 1.559 | 0.957-2.539 | 0.004 | 1.942 | 1.238-3.048 | |
TT | 12(2.8) | 11(4.9) | 8(7.3) | 0.181 | 1.756 | 0.762-4.046 | 0.365 | 1.541 | 0.601-3.949 | 0.028 | 2.706 | 1.078-6.796 |
dbSNPS
|
Frequencies (No., %)
|
LTBI.vs.HC
|
TB.vs.LTBI
|
TB.vs.HC
| |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Alleles
|
HC (
n
= 422)
|
LTBI (
n
= 225)
|
TB (
n
= 109)
|
p
|
OR
|
95% CI
|
p
|
OR
|
95% CI
|
p
|
OR
|
95% CI
| |
TLR1_1805 | G | 74(8.7) | 27(6.0) | 12(5.5) | 0.077 | 0.664 | 0.404-1.064 | 0.798 | 0.913 | 0.412-1.908 | 0.115 | 0.606 | 0.323-1.137 |
T | 770(91.3) | 423(94.0) | 206(94.5) | 0.077 | 1.506 | 0.940-2.473 | 0.798 | 1.095 | 0.524-2.425 | 0.115 | 1.650 | 0.880-3.095 | |
rs3804099 | C | 282(33.4) | 145(32.2) | 54(24.8) | 0.665 | 0.947 | 0.736-1.217 | 0.048 | 0.693 | 0.471-1.012 | 0.014 | 0.656 | 0.467-0.921 |
T | 562(66.6) | 305(67.8) | 164(75.2) | 0.665 | 1.055 | 0.859-1.244 | 0.048 | 1.443 | 0.988-2.124 | 0.014 | 1.524 | 1.086-2.139 | |
rs5743708 | A | 840(99.5) | 441(98.0) | 212(96.8) | 0.009 | 0.233 | 0.052-0.843 | 0.538 | 0.721 | 0.226-2.500 | 0.002 | 0.168 | 0.047-0.602a |
G | 4(0.5) | 9(2.0) | 6(3.2) | 0.009 | 4.291 | 1.187-19.13 | 0.538 | 1.386 | 0.401-4.429 | 0.002 | 5.943 | 1.662-21.25a | |
rs3804100 | C | 252(29.9) | 180(40.0) | 86(39.4) | <0.001 | 1.566 | 1.223-2.003a | 0.892 | 0.977 | 0.692-1.378 | 0.007 | 1.531 | 1.124-2.085 |
T | 592(70.1) | 270(60.0) | 132(60.0) | <0.001 | 0.638 | 0.499-0.818a | 0.892 | 1.023 | 0.742-1.387 | 0.007 | 0.653 | 0.480-0.890 | |
rs1898830 | A | 480(56.9) | 249(55.3) | 120(55.0) | 0.595 | 0.939 | 0.741-1/191 | 0.944 | 0.988 | 0.705-1.387 | 0.628 | 0.929 | 0.688-1.253 |
G | 364(43.1) | 201(44.7) | 98(45.0) | 0.595 | 1.064 | 0.840-1.349 | 0.944 | 1.012 | 0.721-1.419 | 0.628 | 1.077 | 0.798-1.453 | |
rs4986790 | A | 767(90.9) | 404(89.8) | 185(84.9) | 0.521 | 0.882 | 0.591-1.325 | 0.065 | 0.638 | 0.385-1.068 | 0.009 | 0.563 | 0.363-0.872 |
G | 77(9.1) | 46(10.2) | 33(15.1) | 0.521 | 1.133 | 0.754-1.691 | 0.065 | 1.567 | 0.937-2.595 | 0.009 | 1.777 | 1.146-2.754 | |
rs4986791 | C | 760(90.0) | 401(89.1) | 180(82.6) | 0.597 | 1.104 | 0.690-1.556 | 0.018 | 0.579 | 0.309-0.838a | 0.002 | 0.524 | 0.345-0.794a |
T | 84(10.0) | 49(10.9) | 38(17.4) | 0.597 | 0.905 | 0.642-1.449 | 0.018 | 1.727 | 1.193-3.235a | 0.002 | 1.910 | 1.260-2.896a | |
rs11536889 | C | 235(27.8) | 120(26.7) | 60(72.5) | 0.651 | 0.942 | 0.721-1.228 | 0.815 | 1.044 | 0.712-1.523 | 0.925 | 0.984 | 0.705-1.373 |
G | 609(72.2) | 330(73.3) | 158(27.5) | 0.651 | 1.061 | 0.814-1.386 | 0.815 | 0.958 | 0.657-1.404 | 0.925 | 1.016 | 0.728-1.418 | |
rs10759932 | C | 252(29.9) | 132(29.3) | 59(27.1) | 0.844 | 0.975 | 0.752-1.262 | 0.543 | 0.894 | 0.611-1.300 | 0.419 | 0.872 | 0.625-1.216 |
T | 592(70.1) | 318(70.7) | 159(72.9) | 0.844 | 1.026 | 0.792-1.330 | 0.543 | 1.119 | 0.769-1.637 | 0.419 | 1.147 | 0.822-1.601 | |
rs7873784 | C | 193(22.9) | 95(21.1) | 32(14.7) | 0.469 | 0.903 | 0.713-1.270 | 0.047 | 0.643 | 0.401-0.912 | 0.008 | 1.632 | 1.084-2.456 |
G | 651(77.1) | 355(78.9) | 186(85.3) | 0.469 | 1.107 | 0.787-1.403 | 0.047 | 1.555 | 1.017-2.494 | 0.008 | 0.613 | 0.407-0.923 | |
rs10759931 | A | 501(59.4) | 293(65.1) | 142(65.1) | 0.043 | 1.278 | 0.910-1.488 | 0.995 | 1.001 | 0.704-1.429 | 0.120 | 1.164 | 0.853-10589 |
G | 343(40.6) | 157(34.9) | 76(34.9) | 0.043 | 0.782 | 0.672-1.099 | 0.995 | 0.999 | 0.700-1.421 | 0.120 | 0.859 | 0.629-1.173 | |
rs5743810 | C | 12(1.4) | 8(1.8) | 5(2.3) | 0.621 | 1.255 | 0.441-3.366 | 0.710 | 1.238 | 0.330-4.557 | 0.361 | 1.628 | 0.567-4.670 |
T | 832(98.6) | 442(98.2) | 213(97.7) | 0.621 | 0.197 | 0.297-2.265 | 0.710 | 0.807 | 0.219-3.034 | 0.361 | 0.614 | 0.214-1.763 | |
TLR_129 | C | 456(54.0) | 258(57.3) | 145(66.5) | 0.255 | 1.143 | 0.774-1.251 | 0.023 | 1.478 | 0.674-1.335 | 0.001 | 0.932 | 0.689-1.261a |
G | 388(46.0) | 192(42.7) | 73(33.5) | 0.255 | 0.875 | 0.799-1.292 | 0.023 | 0.676 | 0.749-1.484 | 0.001 | 1.073 | 0.793-1.451a | |
rs5743836 | C | 231(27.4) | 151(35.6) | 61(28.0) | 0.020 | 1.340 | 1.038-1.728 | 0.147 | 0.769 | 0.530-1.111 | 0.857 | 1.031 | 0.740-1.437 |
T | 613(72.6) | 299(66.4) | 157(72.0) | 0.020 | 0.746 | 0.579-0.964 | 0.147 | 1.300 | 0.900-1.888 | 0.857 | 0.970 | 0.696-1.352 | |
rs1870884 | C | 113(13.4) | 58(12.9) | 27(12.4) | 0.800 | 0.957 | 0.669-1.359 | 0.855 | 0.955 | 0.563-1.591 | 0.696 | 0.914 | 0.584-1.433 |
T | 731(86.6) | 392(87.1) | 191(87.6) | 0.800 | 1.044 | 0.736-1.494 | 0.855 | 1.047 | 0.629-1.777 | 0.696 | 1.094 | 0.698-1.713 | |
TIRAP_975 | C | 723(85.7) | 367(81.6) | 162(74.3) | 0.053 | 0.740 | 0.539-1.019 | 0.031 | 0.654 | 0.438-0.983a | <0.001 | 0.484 | 0.338-0.694a |
T | 121(14.3) | 83(18.4) | 56(25.7) | 0.053 | 1.351 | 0.981-1.855 | 0.031 | 1.535 | 1.017-2.286a | <0.001 | 2.066 | 1.442-2.960a |
Haplotype analysis
SNP marker
|
Haplotype
|
Frequency (No., %)
|
LTBI.vs.HC
|
PTB.vs.LTBI
| ||||||
---|---|---|---|---|---|---|---|---|---|---|
HC (
n
= 422)
|
LTBI (
n
= 225)
|
PTB (
n
= 109)
|
P
|
OR
|
95% CI
|
P
|
OR
|
95% CI
| ||
rs3804099 | CC | 183(21.7) | 95(21.1) | 52(23.8) | 0.812 | 0.97 | 0.722-1.289 | 0.422 | 1.17 | 0.779-1.747 |
rs3804100 | CT | 185(21.9) | 85(18.9) | 36(16.5) | 0.201 | 0.83 | 0.615-1.114 | 0.455 | 0.85 | 0.537-1.326 |
TC | 103(12.2) | 56(12.4) | 18(8.3) | 0.900 | 1.02 | 0.709-1.465 | 0.106 | 0.63 | 0.341-1.129 | |
TT | 373(44.2) | 214(47.6) | 112(51.4) | 0.247 | 1.15 | 0.904-1.450 | 0.354 | 1.17 | 0.832-1.632 | |
rs10759931 | AT | 376(44.4) | 204(45.3) | 136(62.4) | 0.787 | 1.03 | 0.735-1.447 | <0.001a | 2.00 | 1.221-3.289 |
rs10759932 | GT | 218(25.7) | 112(24.9) | 22(10.1) | 0.712 | 0.95 | 0.642-1.401 | <0.001a | 0.34 | 0.153-0.694 |
GC | 156(18.5) | 88(19.6) | 6(2.8) | 0.639 | 1.07 | 0.693-1.646 | <0.001a | 0.12 | 0.022-0.379 | |
AC | 94(11.4) | 46(10.2) | 54(24.7) | 0.614 | 0.91 | 0.511-1.578 | <0.001a | 2.89 | 1.496-5.596 | |
rs4986790 | AC | 644(76.3) | 353(78.4) | 157(72.0) | 0.383 | 1.13 | 0.852-1.505 | 0.067 | 0.71 | 0.481-1.046 |
rs4986791 | AT | 49(5.8) | 11(2.4) | 18(8.3) | 0.006 | 0.39 | 0.180-0.784 | 0.001a | 3.59 | 1.570-8.565 |
GC | 33(3.9) | 9(2.0) | 0(0) | 0.065 | 0.50 | 0.209-1.083 | - | - | - | |
GT | 118(14.0) | 77(17.1) | 43(19.7) | 0.134 | 1.27 | 0.915-1.755 | 0.409 | 1.19 | 0.766-1.833 |
Gene–gene and gene–environment interactions evaluated with nonparametric MDR
Best model
|
Testing accuracy
|
Testing sensitivity
|
Testing OR
|
Testing χ2
|
p
|
Cross-validation consistency
|
---|---|---|---|---|---|---|
PTB.vs.LTBI | ||||||
BCG | 0.61 | 0.70 | 1.76(1.067-2.903)a | 4.958 | 0.026a | 6/10 |
rs10759932, rs7873784 | 0.76 | 0.72 | 3.29(2.096-8.283)a | 9.253 | 0.0024a | 10/10 |
rs10759932, rs7873784, rs10759931 | 0.84 | 0.81 | 5.67(3.158-14.99)a | 12.67 | 0.0004a | 10/10 |
LTBI.vs.HC | ||||||
rs5743836 | 0.56 | 0.55 | 1.68(1.189-2.365)a | 8.76 | 0.0031a | 9/10 |
rs3804100, rs1898830 | 0.69 | 0.63 | 4.57(1.532-13.61)a | 7.88 | 0.005a | 10/10 |
rs3804100, rs1898830, rs10759931 | 0.80 | 0.79 | 5.76(3.332-16.07)a | 21.85 | 0.0001a | 10/10 |