Background
Methods
Patients and samples
Genotyping
Gene rs-number | Healthy controls | AS | Unadjusted | Adjusted, age & sex | Adjusted, age, sex & smoking | |||
---|---|---|---|---|---|---|---|---|
OR (95 CI) |
p
| OR (9 5CI) |
p
| OR (95 CI) |
p
| |||
TLR1
rs4833095 | ||||||||
TT | 485 | 415 | ||||||
TC | 261 | 238 | 1.07 (0.86–1.33) | 0.57 | 1.03 (0.82–1.29) | 0.83 | 1.05 (0.78–1.42) | 0.73 |
CC | 20 | 43 | 2.51 (1.45–4.34) | 0.00095 | 2.59 (1.48–4.51) | 0.00081 | 2.86 (1.44–5.68) | 0.0026 |
TC or CC | 281 | 281 | 1.17 (0.95–1.44) | 0.15 | 1.14 (0.91–1.41) | 0.25 | 1.18 (0.89–1.58) | 0.26 |
TLR2
rs3804099 | ||||||||
TT | 241 | 197 | ||||||
TC | 393 | 354 | 1.10 (0.87–1.40) | 0.42 | 1.07 (0.84–1.37) | 0.58 | 1.02 (0.73–1.42) | 0.90 |
CC | 144 | 142 | 1.21 (0.89–1.63) | 0.22 | 1.24 (0.91–1.68) | 0.17 | 1.30 (0.87–1.96) | 0.20 |
TC or CC | 537 | 496 | 1.13 (0.90–1.41) | 0.29 | 1.11 (0.89–1.40) | 0.36 | 1.10 (0.80–1.50) | 0.57 |
TLR2
rs11938228 | ||||||||
CC | 327 | 314 | ||||||
CA | 368 | 313 | 0.89 (0.71–1.10) | 0.27 | 0.86 (0.69–1.07) | 0.17 | 0.80 (0.60–1.08) | 0.15 |
AA | 76 | 69 | 0.95 (0.66–1.36) | 0.76 | 0.92 (0.63–1.33) | 0.66 | 1.03 (0.62–1.69) | 0.92 |
CA or AA | 444 | 382 | 0.90 (0.73–1.10) | 0.30 | 0.87 (0.70–1.07) | 0.19 | 0.84 (0.63–1.11) | 0.22 |
TLR2
rs4696480 | ||||||||
AA | 199 | 179 | ||||||
AT | 417 | 348 | 0.93 (0.72–1.19) | 0.55 | 0.89 (0.69–1.15) | 0.38 | 0.84 (0.60–1.18) | 0.31 |
TT | 155 | 169 | 1.21 (0.90–1.63) | 0.20 | 1.16 (0.86–1.58) | 0.33 | 1.18 (0.78–1.78) | 0.44 |
AT or TT | 572 | 517 | 1.00 (0.79–1.27) | 0.97 | 0.97 (0.76–1.23) | 0.78 | 0.92 (0.67–1.27) | 0.62 |
TLR4
rs5030728 | ||||||||
GG | 359 | 322 | ||||||
GA | 323 | 298 | 1.03 (0.83–1.28) | 0.80 | 1.01 (0.81–1.27) | 0.91 | 0.93 (0.69–1.25) | 0.62 |
AA | 78 | 70 | 1.00 (0.70–1.43) | 1.00 | 0.98 (0.68–1.42) | 0.93 | 0.87 (0.53–1.42) | 0.57 |
GA or AA | 401 | 368 | 1.02 (0.83–1.26) | 0.83 | 1.01 (0.82–1.25) | 0.94 | 0.91 (0.69–1.21) | 0.53 |
TLR4
rs1554973 | ||||||||
TT | 440 | 395 | ||||||
TC | 272 | 261 | 1.07 (0.86–1.33) | 0.55 | 1.06 (0.85–1.32) | 0.62 | 0.98 (0.73–1.32) | 0.90 |
CC | 62 | 33 | 0.59 (0.38–0.92) | 0.02 | 0.55 (0.34–0.86) | 0.01 | 0.68 (0.38–1.23) | 0.20 |
TC or CC | 334 | 294 | 0.98 (0.80–1.21) | 0.85 | 0.96 (0.78–1.19) | 0.72 | 0.93 (0.70–1.24) | 0.63 |
TLR4
rs12377632 | ||||||||
TT | 306 | 271 | ||||||
TC | 358 | 319 | 1.01 (0.81–1.26) | 0.96 | 1.05 (0.84–1.32) | 0.66 | 1.07 (0.78–1.46) | 0.67 |
CC | 102 | 96 | 1.06 (0.77–1.47) | 0.71 | 1.11 (0.80–1.55) | 0.52 | 1.41 (0.92–2.17) | 0.12 |
TC or CC | 460 | 415 | 1.02 (0.83–1.26) | 0.86 | 1.06 (0.86–1.32) | 0.58 | 1.14 (0.85–1.53) | 0.37 |
TLR5
rs5744168 | ||||||||
CC | 672 | 605 | ||||||
CT | 94 | 89 | 1.05 (0.77–1.43) | 0.75 | 1.05 (0.77–1.45) | 0.74 | 0.89 (0.58–1.37) | 0.60 |
TT | 5 | 2 | 0.44 (0.09–2.30) | 0.33 | 0.45 (0.08–2.43) | 0.35 | 0.04 (0.00–3.54) | 0.16 |
CT or TT | 99 | 91 | 1.02 (0.75–1.39) | 0.89 | 1.02 (0.75–1.40) | 0.88 | 0.84 (0.55–1.29) | 0.43 |
TLR5
rs5744174 | ||||||||
TT | 215 | 216 | ||||||
TC | 399 | 337 | 0.84 (0.66–1.07) | 0.15 | 0.85 (0.67–1.09) | 0.20 | 0.82 (0.60–1.14) | 0.24 |
CC | 144 | 138 | 0.95 (0.71–1.29) | 0.76 | 1.02 (0.75–1.39) | 0.91 | 0.87 (0.57–1.32) | 0.51 |
TC or CC | 543 | 475 | 0.87 (0.69–1.09) | 0.23 | 0.90 (0.71–1.13) | 0.36 | 0.84 (0.62–1.14) | 0.26 |
TLR9
rs187084 | ||||||||
TT | 262 | 237 | ||||||
TC | 366 | 335 | 1.01 (0.80–1.27) | 0.92 | 1.03 (0.82–1.31) | 0.78 | 1.09 (0.79–1.50) | 0.60 |
CC | 142 | 120 | 0.93 (0.69–1.26) | 0.66 | 0.91 (0.67–1.24) | 0.56 | 1.07 (0.71–1.61) | 0.76 |
TC or CC | 508 | 455 | 0.99 (0.80–1.23) | 0.93 | 1.00 (0.80–1.25) | 0.98 | 1.08 (0.80–1.46) | 0.60 |
TLR9
rs352139 | ||||||||
GG | 255 | 211 | ||||||
GA | 347 | 324 | 1.13 (0.89–1.43) | 0.32 | 1.08 (0.85–1.38) | 0.52 | 1.01 (0.73–1.40) | 0.93 |
AA | 167 | 139 | 1.01 (0.75–1.34) | 0.97 | 0.96 (0.71–1.30) | 0.79 | 0.80 (0.53–1.20) | 0.27 |
GA or AA | 514 | 463 | 1.09 (0.87–1.36) | 0.45 | 1.04 (0.83–1.31) | 0.72 | 0.94 (0.69–1.27) | 0.68 |
LY96
rs11465996 | ||||||||
CC | 344 | 341 | ||||||
CG | 337 | 298 | 0.89 (0.72–1.11) | 0.30 | 0.91 (0.73–1.14) | 0.42 | 0.89 (0.66–1.20) | 0.45 |
GG | 81 | 53 | 0.66 (0.45–0.96) | 0.03 | 0.68 (0.46–1.00) | 0.0498 | 0.65 (0.39–1.10) | 0.11 |
CG or GG | 418 | 351 | 0.85 (0.69–1.04) | 0.11 | 0.87 (0.70–1.07) | 0.18 | 0.84 (0.63–1.12) | 0.24 |
CD14
Rs2569190 | ||||||||
GG | 236 | 194 | ||||||
GA | 360 | 339 | 1.15 (0.90–1.46) | 0.27 | 1.18 (0.92–1.51) | 0.19 | 1.27 (0.91–1.78) | 0.16 |
AA | 170 | 157 | 1.12 (0.84–1.50) | 0.43 | 1.20 (0.89–1.61) | 0.24 | 1.46 (0.98–2.19) | 0.06 |
GA or AA | 530 | 496 | 1.14 (0.91–1.43) | 0.26 | 1.18 (0.94–1.50) | 0.15 | 1.32 (0.96–1.82) | 0.08 |
TIRAP
rs8177374 | ||||||||
CC | 556 | 521 | ||||||
CT | 185 | 159 | 0.92 (0.72–1.17) | 0.49 | 0.99 (0.77–1.27) | 0.94 | 1.38 (0.99–1.91) | 0.06 |
TT | 21 | 15 | 0.76 (0.39–1.49) | 0.43 | 0.76 (0.38–1.53) | 0.45 | 1.31 (0.55–3.12) | 0.55 |
CT or TT | 206 | 174 | 0.90 (0.71–1.14) | 0.39 | 0.97 (0.76–1.23) | 0.81 | 1.38 (1.00–1.89) | 0.047 |
SUMO4
rs237025 | ||||||||
TT | 215 | 195 | ||||||
TC | 362 | 358 | 1.09 (0.86–1.39) | 0.48 | 1.08 (0.84–1.38) | 0.55 | 1.04 (0.75–1.44) | 0.80 |
CC | 195 | 136 | 0.77 (0.57–1.03) | 0.08 | 0.75 (0.55–1.01) | 0.06 | 0.55 (0.36–0.84) | 0.01 |
TC or CC | 557 | 494 | 0.98 (0.78–1.23) | 0.85 | 0.96 (0.76–1.22) | 0.75 | 0.87 (0.64–1.19) | 0.38 |
NFKBIA
rs696 | ||||||||
GG | 298 | 259 | ||||||
GA | 366 | 336 | 1.06 (0.85–1.32) | 0.63 | 1.06 (0.84–1.33) | 0.64 | 1.02 (0.75–1.39) | 0.88 |
AA | 101 | 90 | 1.03 (0.74–1.43) | 0.88 | 0.97 (0.69–1.36) | 0.86 | 1.07 (0.67–1.69) | 0.78 |
GA or AA | 467 | 426 | 1.05 (0.85–1.30) | 0.65 | 1.04 (0.84–1.29) | 0.73 | 1.03 (0.77–1.38) | 0.84 |
NFKB1
rs28362491 | ||||||||
Ins/Ins | 269 | 258 | ||||||
Ins/− | 376 | 316 | 0.88 (0.70–1.10) | 0.25 | 0.89 (0.70–1.12) | 0.31 | 0.74 (0.54–1.01) | 0.06 |
−/− | 122 | 100 | 0.85 (0.62–1.17) | 0.33 | 0.82 (0.59–1.13) | 0.22 | 0.78 (0.51–1.19) | 0.25 |
Ins/− or −/− | 498 | 416 | 0.87 (0.70–1.08) | 0.21 | 0.87 (0.70–1.08) | 0.21 | 0.75 (0.56–1.01) | 0.06 |
TNF
rs1800629 | ||||||||
GG | 527 | 549 | ||||||
GA | 223 | 129 | 0.56 (0.43–0.71) | 0.0000032 | 0.58 (0.45–0.75) | 0.000029 | 0.63 (0.45–0.89) | 0.01 |
AA | 25 | 9 | 0.35 (0.16–0.75) | 0.01 | 0.39 (0.18–0.85) | 0.02 | 0.19 (0.04–0.79) | 0.02 |
GA or AA | 248 | 138 | 0.53 (0.42–0.68) | 0.00000030 | 0.56 (0.44–0.72) | 0.0000047 | 0.59 (0.42–0.82) | 0.0018 |
TNF
rs361525 | ||||||||
GG | 708 | 669 | ||||||
GA | 60 | 30 | 0.53 (0.34–0.83) | 0.01 | 0.52 (0.32–0.82) | 0.0049 | 0.61 (0.33–1.12) | 0.11 |
AA | 3 | 0 | 1.00 (1.00–1.00) | 1.00 | 1.00 (1.00–1.00) | 1.00 | 1.00 (1.00–1.00) | 1.00 |
GA or AA | 63 | 30 | 0.50 (0.32–0.79) | 0.0027 | 0.49 (0.31–0.78) | 0.0024 | 0.58 (0.32–1.05) | 0.07 |
TNFRSF1A
rs4149570 | ||||||||
GG | 307 | 217 | ||||||
GT | 355 | 339 | 1.35 (1.07–1.70) | 0.01 | 1.33 (1.05–1.68) | 0.02 | 1.46 (1.06–2.00) | 0.02 |
TT | 109 | 132 | 1.71 (1.26–2.33) | 0.00060 | 1.79 (1.31–2.46) | 0.00027 | 2.26 (1.48–3.47) | 0.00017 |
GT or TT | 464 | 471 | 1.44 (1.16–1.78) | 0.0010 | 1.44 (1.15–1.80) | 0.0013 | 1.64 (1.21–2.22) | 0.0014 |
TNFAIP3
rs6927172 | ||||||||
CC | 473 | 415 | ||||||
CG | 264 | 245 | 1.06 (0.85–1.32) | 0.61 | 1.06 (0.85–1.33) | 0.61 | 1.03 (0.76–1.39) | 0.85 |
GG | 40 | 25 | 0.71 (0.42–1.19) | 0.20 | 0.70 (0.41–1.19) | 0.18 | 0.51 (0.23–1.10) | 0.09 |
CG or GG | 304 | 270 | 1.01 (0.82–1.25) | 0.91 | 1.01 (0.82–1.26) | 0.91 | 0.95 (0.71–1.27) | 0.73 |
TGFB1
rs1800469 | ||||||||
CC | 383 | 344 | ||||||
CT | 297 | 299 | 1.12 (0.90–1.39) | 0.30 | 1.08 (0.87–1.35) | 0.48 | 1.28 (0.95–1.71) | 0.11 |
TT | 86 | 53 | 0.69 (0.47–1.00) | 0.047 | 0.69 (0.47–1.02) | 0.06 | 0.69 (0.40–1.17) | 0.17 |
CT or TT | 383 | 352 | 1.02 (0.83–1.26) | 0.83 | 1.00 (0.81–1.23) | 0.97 | 1.14 (0.86–1.52) | 0.35 |
PTPN22
rs2476601 | ||||||||
GG | 588 | 557 | ||||||
GA | 166 | 122 | 0.78 (0.60–1.01) | 0.06 | 0.77 (0.59–1.00) | 0.05 | 0.75 (0.52–1.09) | 0.13 |
AA | 11 | 6 | 0.58 (0.21–1.57) | 0.28 | 0.57 (0.20–1.58) | 0.28 | 0.83 (0.21–3.28) | 0.80 |
GA or AA | 177 | 128 | 0.76 (0.59–0.99) | 0.04 | 0.76 (0.58–0.98) | 0.04 | 0.76 (0.53–1.09) | 0.13 |
PPARG
rs1801282 | ||||||||
CC | 548 | 511 | ||||||
CG | 207 | 167 | 0.87 (0.68–1.10) | 0.23 | 0.85 (0.66–1.08) | 0.18 | 0.87 (0.63–1.21) | 0.42 |
GG | 14 | 15 | 1.15 (0.55–2.40) | 0.71 | 1.33 (0.62–2.83) | 0.46 | 1.54 (0.60–3.98) | 0.37 |
CG or GG | 221 | 182 | 0.88 (0.70–1.11) | 0.29 | 0.88 (0.69–1.11) | 0.27 | 0.91 (0.67–1.26) | 0.58 |
IL1B
rs4848306 | ||||||||
GG | 246 | 215 | ||||||
GA | 373 | 352 | 1.08 (0.85–1.36) | 0.52 | 1.09 (0.86–1.39) | 0.48 | 1.16 (0.84–1.60) | 0.38 |
AA | 151 | 125 | 0.95 (0.70–1.28) | 0.72 | 0.96 (0.71–1.31) | 0.81 | 0.88 (0.57–1.34) | 0.55 |
GA or AA | 524 | 477 | 1.04 (0.83–1.30) | 0.72 | 1.06 (0.84–1.33) | 0.64 | 1.08 (0.79–1.46) | 0.64 |
IL1B
rs1143623 | ||||||||
GG | 401 | 365 | ||||||
GC | 316 | 278 | 0.97 (0.78–1.20) | 0.76 | 0.98 (0.79–1.22) | 0.87 | 1.07 (0.80–1.44) | 0.66 |
CC | 55 | 52 | 1.04 (0.69–1.56) | 0.85 | 1.12 (0.74–1.69) | 0.59 | 0.87 (0.48–1.57) | 0.64 |
GC or CC | 371 | 330 | 0.98 (0.80–1.20) | 0.83 | 1.00 (0.81–1.24) | 0.98 | 1.04 (0.78–1.38) | 0.79 |
IL1B
rs1143627 | ||||||||
TT | 340 | 305 | ||||||
TC | 339 | 305 | 1.00 (0.81–1.25) | 0.98 | 1.00 (0.79–1.25) | 0.97 | 1.05 (0.78–1.42) | 0.75 |
CC | 97 | 86 | 0.99 (0.71–1.37) | 0.94 | 1.01 (0.72–1.41) | 0.95 | 0.85 (0.53–1.36) | 0.50 |
TC or CC | 436 | 391 | 1.00 (0.81–1.23) | 1.00 | 1.00 (0.81–1.24) | 1.00 | 1.00 (0.76–1.34) | 0.97 |
IL1RN
rs4251961 | ||||||||
TT | 298 | 247 | ||||||
TC | 360 | 324 | 1.09 (0.87–1.36) | 0.47 | 1.04 (0.83–1.32) | 0.71 | 1.22 (0.89–1.67) | 0.21 |
CC | 112 | 105 | 1.13 (0.83–1.55) | 0.44 | 1.05 (0.76–1.46) | 0.76 | 1.41 (0.92–2.17) | 0.12 |
TC or CC | 472 | 429 | 1.10 (0.89–1.36) | 0.40 | 1.05 (0.84–1.30) | 0.68 | 1.26 (0.94–1.71) | 0.12 |
IL4R
rs1805010 | ||||||||
AA | 209 | 201 | ||||||
AG | 410 | 317 | 0.80 (0.63–1.02) | 0.08 | 0.79 (0.62–1.02) | 0.07 | 0.73 (0.52–1.02) | 0.07 |
GG | 157 | 133 | 0.88 (0.65–1.19) | 0.41 | 0.91 (0.67–1.24) | 0.55 | 0.87 (0.58–1.33) | 0.53 |
AG or GG | 567 | 450 | 0.83 (0.66–1.04) | 0.10 | 0.83 (0.65–1.05) | 0.12 | 0.77 (0.56–1.06) | 0.11 |
IL6
rs10499563 | ||||||||
TT | 476 | 439 | ||||||
TC | 259 | 225 | 0.94 (0.76–1.17) | 0.60 | 0.94 (0.75–1.18) | 0.60 | 0.77 (0.57–1.05) | 0.10 |
CC | 35 | 26 | 0.81 (0.48–1.36) | 0.42 | 0.72 (0.42–1.25) | 0.24 | 0.80 (0.39–1.63) | 0.53 |
TC or CC | 294 | 251 | 0.93 (0.75–1.14) | 0.48 | 0.92 (0.74–1.14) | 0.43 | 0.77 (0.57–1.04) | 0.09 |
IL6R
rs4537545 | ||||||||
CC | 289 | 247 | ||||||
CT | 369 | 324 | 1.03 (0.82–1.29) | 0.82 | 1.05 (0.83–1.32) | 0.71 | 1.07 (0.79–1.47) | 0.65 |
TT | 117 | 113 | 1.13 (0.83–1.54) | 0.44 | 1.18 (0.86–1.63) | 0.30 | 1.17 (0.76–1.79) | 0.48 |
CT or TT | 486 | 437 | 1.05 (0.85–1.30) | 0.64 | 1.08 (0.86–1.34) | 0.51 | 1.09 (0.81–1.47) | 0.55 |
IL10
rs1800872 | ||||||||
CC | 482 | 408 | ||||||
CA | 258 | 225 | 1.03 (0.83–1.29) | 0.79 | 1.01 (0.80–1.27) | 0.94 | 0.93 (0.68–1.26) | 0.63 |
AA | 35 | 42 | 1.42 (0.89–2.26) | 0.14 | 1.35 (0.83–2.18) | 0.22 | 1.47 (0.79–2.73) | 0.22 |
CA or AA | 293 | 267 | 1.08 (0.87–1.33) | 0.50 | 1.05 (0.84–1.30) | 0.67 | 0.99 (0.74–1.33) | 0.95 |
IL10
rs3024505 | ||||||||
CC | 518 | 467 | ||||||
CT | 221 | 200 | 1.00 (0.80–1.26) | 0.97 | 1.01 (0.80–1.28) | 0.95 | 1.19 (0.87–1.61) | 0.28 |
TT | 22 | 24 | 1.21 (0.67–2.19) | 0.53 | 1.32 (0.72–2.42) | 0.37 | 1.80 (0.79–4.12) | 0.16 |
CT or TT | 243 | 224 | 1.02 (0.82–1.27) | 0.84 | 1.04 (0.83–1.30) | 0.76 | 1.23 (0.92–1.66) | 0.17 |
IL12B
rs3212217 | ||||||||
GG | 499 | 460 | ||||||
GC | 235 | 200 | 0.92 (0.74–1.16) | 0.49 | 0.95 (0.75–1.19) | 0.64 | 0.94 (0.69–1.29) | 0.72 |
CC | 25 | 21 | 0.91 (0.50–1.65) | 0.76 | 0.94 (0.51–1.72) | 0.84 | 0.57 (0.23–1.41) | 0.22 |
GC or CC | 260 | 221 | 0.92 (0.74–1.15) | 0.47 | 0.95 (0.76–1.19) | 0.63 | 0.91 (0.67–1.23) | 0.53 |
IL12B
rs6887695 | ||||||||
GG | 385 | 324 | ||||||
GC | 293 | 301 | 1.22 (0.98–1.52) | 0.07 | 1.24 (0.99–1.55) | 0.06 | 1.31 (0.97–1.77) | 0.07 |
CC | 72 | 70 | 1.16 (0.81–1.66) | 0.43 | 1.16 (0.80–1.69) | 0.43 | 0.98 (0.59–1.61) | 0.94 |
GC or CC | 365 | 371 | 1.21 (0.98–1.49) | 0.07 | 1.22 (0.99–1.51) | 0.06 | 1.24 (0.93–1.64) | 0.14 |
IL12RB1
rs401502 | ||||||||
CC | 360 | 304 | ||||||
CG | 303 | 311 | 1.22 (0.98–1.51) | 0.08 | 1.21 (0.96–1.51) | 0.10 | 1.19 (0.88–1.61) | 0.26 |
GG | 87 | 70 | 0.95 (0.67–1.35) | 0.79 | 0.97 (0.68–1.39) | 0.87 | 1.18 (0.74–1.88) | 0.48 |
CG or GG | 390 | 381 | 1.16 (0.94–1.42) | 0.17 | 1.15 (0.93–1.43) | 0.19 | 1.19 (0.89–1.58) | 0.24 |
IL17A
rs2275913 | ||||||||
GG | 340 | 307 | ||||||
GA | 336 | 301 | 0.99 (0.80–1.24) | 0.94 | 0.98 (0.79–1.23) | 0.89 | 0.90 (0.67–1.22) | 0.51 |
AA | 95 | 84 | 0.98 (0.70–1.36) | 0.90 | 1.00 (0.71–1.40) | 0.98 | 1.00 (0.63–1.57) | 0.99 |
GA or AA | 431 | 385 | 0.99 (0.80–1.22) | 0.92 | 0.99 (0.80–1.22) | 0.89 | 0.92 (0.69–1.22) | 0.57 |
IL18
rs187238 | ||||||||
GG | 387 | 380 | ||||||
GC | 312 | 259 | 0.85 (0.68–1.05) | 0.13 | 0.83 (0.66–1.03) | 0.09 | 0.74 (0.55–1.00) | 0.049 |
CC | 64 | 41 | 0.65 (0.43–0.99) | 0.04 | 0.69 (0.45–1.06) | 0.09 | 0.58 (0.32–1.04) | 0.07 |
GC or CC | 376 | 300 | 0.81 (0.66–1.00) | 0.0499 | 0.80 (0.65–0.99) | 0.04 | 0.71 (0.53–0.95) | 0.02 |
IL18
rs1946518 | ||||||||
GG | 282 | 259 | ||||||
GT | 363 | 329 | 0.99 (0.79–1.24) | 0.91 | 0.96 (0.76–1.21) | 0.71 | 0.89 (0.65–1.21) | 0.45 |
TT | 113 | 97 | 0.93 (0.68–1.29) | 0.68 | 0.95 (0.68–1.31) | 0.74 | 0.80 (0.51–1.24) | 0.32 |
GT or TT | 476 | 426 | 0.97 (0.79–1.21) | 0.81 | 0.96 (0.77–1.19) | 0.68 | 0.86 (0.64–1.16) | 0.32 |
IL23R
rs11209026 | ||||||||
GG | 680 | 646 | ||||||
GA | 89 | 50 | 0.59 (0.41–0.85) | 0.0045 | 0.63 (0.43–0.91) | 0.02 | 0.64 (0.38–1.05) | 0.08 |
AA | 5 | 1 | 1.00 (1.00–1.00) | 1.00 | 1.00 (1.00–1.00) | 1.00 | 1.00 (1.00–1.00) | 1.00 |
GA or AA | 94 | 51 | 0.57 (0.40–0.82) | 0.0021 | 0.60 (0.42–0.87) | 0.01 | 0.63 (0.38–1.03) | 0.06 |
IFNG
rs2430561 | ||||||||
TT | 199 | 181 | ||||||
TA | 398 | 369 | 1.02 (0.80–1.30) | 0.88 | 1.01 (0.79–1.30) | 0.92 | 1.08 (0.77–1.52) | 0.65 |
AA | 161 | 139 | 0.95 (0.70–1.29) | 0.74 | 0.97 (0.71–1.32) | 0.85 | 1.09 (0.72–1.64) | 0.68 |
TA or AA | 559 | 508 | 1.00 (0.79–1.26) | 0.99 | 1.00 (0.79–1.27) | 0.99 | 1.08 (0.79–1.50) | 0.62 |
IFNGR1
rs2234711 | ||||||||
TT | 290 | 232 | ||||||
TC | 361 | 348 | 1.20 (0.96–1.51) | 0.11 | 1.20 (0.95–1.51) | 0.12 | 1.15 (0.84–1.57) | 0.40 |
CC | 119 | 108 | 1.13 (0.83–1.55) | 0.43 | 1.09 (0.79–1.50) | 0.60 | 1.11 (0.72–1.70) | 0.65 |
TC or CC | 480 | 456 | 1.19 (0.96–1.47) | 0.12 | 1.17 (0.94–1.46) | 0.16 | 1.14 (0.84–1.53) | 0.40 |
IFNGR2
rs8126756 | ||||||||
TT | 553 | 522 | ||||||
TC | 168 | 130 | 0.82 (0.63–1.06) | 0.13 | 0.83 (0.64–1.09) | 0.18 | 0.86 (0.60–1.24) | 0.42 |
CC | 18 | 12 | 0.71 (0.34–1.48) | 0.36 | 0.69 (0.32–1.49) | 0.35 | 0.53 (0.18–1.54) | 0.24 |
TC or CC | 186 | 142 | 0.81 (0.63–1.04) | 0.09 | 0.82 (0.64–1.06) | 0.13 | 0.83 (0.59–1.17) | 0.28 |
IFNGR2
rs17882748 | ||||||||
CC | 199 | 173 | ||||||
CT | 391 | 341 | 1.00 (0.78–1.29) | 0.98 | 1.00 (0.77–1.30) | 0.99 | 1.01 (0.71–1.42) | 0.97 |
TT | 153 | 174 | 1.31 (0.97–1.76) | 0.08 | 1.31 (0.97–1.78) | 0.08 | 1.16 (0.77–1.73) | 0.48 |
CT or TT | 544 | 515 | 1.09 (0.86–1.38) | 0.48 | 1.09 (0.86–1.39) | 0.48 | 1.05 (0.76–1.45) | 0.76 |
TBX21
rs17250932 | ||||||||
TT | 526 | 497 | ||||||
TC | 210 | 179 | 0.90 (0.71–1.14) | 0.39 | 0.94 (0.74–1.19) | 0.61 | 0.84 (0.60–1.17) | 0.30 |
CC | 32 | 19 | 0.63 (0.35–1.12) | 0.12 | 0.66 (0.36–1.19) | 0.17 | 0.37 (0.14–0.98) | 0.046 |
TC or CC | 242 | 198 | 0.87 (0.69–1.08) | 0.21 | 0.90 (0.72–1.14) | 0.39 | 0.78 (0.56–1.07) | 0.12 |
NLRP1
rs2670660 | ||||||||
AA | 222 | 202 | ||||||
AG | 390 | 328 | 0.92 (0.73–1.18) | 0.52 | 0.96 (0.75–1.23) | 0.73 | 1.12 (0.80–1.56) | 0.52 |
GG | 154 | 154 | 1.10 (0.82–1.47) | 0.53 | 1.11 (0.82–1.49) | 0.51 | 1.12 (0.75–1.67) | 0.59 |
AG or GG | 544 | 482 | 0.97 (0.78–1.22) | 0.82 | 1.00 (0.79–1.26) | 0.98 | 1.11 (0.81–1.52) | 0.50 |
NLRP1
rs878329 | ||||||||
GG | 217 | 206 | ||||||
GC | 394 | 333 | 0.89 (0.70–1.13) | 0.34 | 0.89 (0.69–1.14) | 0.35 | 0.99 (0.71–1.38) | 0.93 |
CC | 155 | 155 | 1.05 (0.79–1.41) | 0.73 | 1.05 (0.78–1.41) | 0.75 | 1.03 (0.69–1.54) | 0.90 |
GC or CC | 549 | 488 | 0.94 (0.75–1.17) | 0.57 | 0.93 (0.74–1.18) | 0.56 | 1.00 (0.73–1.36) | 0.98 |
NLRP3
rs10754558 | ||||||||
CC | 294 | 248 | ||||||
CG | 355 | 324 | 1.08 (0.86–1.36) | 0.50 | 1.06 (0.84–1.34) | 0.61 | 1.10 (0.81–1.51) | 0.54 |
GG | 111 | 116 | 1.24 (0.91–1.69) | 0.18 | 1.25 (0.91–1.71) | 0.17 | 1.11 (0.71–1.72) | 0.65 |
CG or GG | 466 | 440 | 1.12 (0.90–1.39) | 0.30 | 1.11 (0.89–1.38) | 0.36 | 1.11 (0.82–1.49) | 0.51 |
NLRP3
rs4612666 | ||||||||
CC | 435 | 360 | ||||||
CT | 280 | 277 | 1.20 (0.96–1.49) | 0.11 | 1.23 (0.99–1.54) | 0.07 | 1.28 (0.95–1.72) | 0.10 |
TT | 53 | 48 | 1.09 (0.72–1.66) | 0.67 | 1.19 (0.78–1.82) | 0.41 | 1.07 (0.59–1.94) | 0.82 |
CT or TT | 333 | 325 | 1.18 (0.96–1.45) | 0.12 | 1.23 (0.99–1.52) | 0.06 | 1.24 (0.94–1.65) | 0.13 |
CARD8
rs2043211 | ||||||||
AA | 321 | 298 | ||||||
AT | 342 | 316 | 1.00 (0.80–1.24) | 0.97 | 0.98 (0.79–1.23) | 0.89 | 0.90 (0.67–1.22) | 0.50 |
TT | 94 | 78 | 0.89 (0.64–1.25) | 0.52 | 0.89 (0.63–1.26) | 0.50 | 0.91 (0.57–1.44) | 0.68 |
AT or TT | 436 | 394 | 0.97 (0.79–1.20) | 0.80 | 0.96 (0.78–1.19) | 0.72 | 0.90 (0.67–1.19) | 0.45 |
JAK2
rs12343867 | ||||||||
TT | 398 | 358 | ||||||
TC | 299 | 263 | 0.98 (0.79–1.22) | 0.84 | 0.96 (0.76–1.20) | 0.69 | 0.82 (0.61–1.12) | 0.21 |
CC | 61 | 65 | 1.18 (0.81–1.73) | 0.38 | 1.11 (0.75–1.63) | 0.61 | 1.03 (0.62–1.71) | 0.91 |
TC or CC | 360 | 328 | 1.01 (0.82–1.25) | 0.90 | 0.98 (0.79–1.21) | 0.86 | 0.86 (0.64–1.14) | 0.29 |
Gene | Rs-number | Pathway | Model | OR (95% CI) | P-value / Bonferronia | Effect of minor-allele | Biological interpretation |
---|---|---|---|---|---|---|---|
TLR1
| rs4833095 | Pathogen recognition | CC vs TT | 2.59 (1.48–4.51) | 0.00081 / 0.04 | 743C increase TLR1 level in PBMC [56] | Increased TLR1 level was associated with increased risk of AS. This could indicate that a genetically determined high activity of the NFkB pathway, and thus high TNF-α and IL-17 activity, was associated with increased risk of AS. |
TLR4
| rs1554973 | Pathogen recognition | CC vs TT | 0.55 (0.34–0.86) | 0.010 / 0.51 | Unknown [67] | – |
LY96
| rs11465996 | Pathogen recognition | GG vs CC | 0.68 (0.46–1.00) | 0.049 / 1.00 | -1625G increase MD-2 and TNF-α levels in human U937 cells and whole blood leukocytes [57] | Increased MD-2 and TNF-α level was associated with a reduced risk of AS. In contrast to the other results this indicate that genetically determined high TNF-driven inflammatory response was associated with reduced risk of AS. |
TNF
| rs1800629 | Cytokines | GA or AA vs GG | 0.56 (0.44–0.72) | 0.0000047 / 0.00024 | Reduced TNF-α mRNA level was associated with reduced risk of AS. This could indicate that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS. | |
TNF
| rs361525 | Cytokines | GA or AA vs GG | 0.49 (0.31–0.78) | 0.0024 / 0.12 | -238A reduce expression in PBMC [49] | Reduced TNF-α expression was associated with reduced risk of AS. This indicates that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS. |
TNFRSF1A
| rs4149570 | Cytokines | GT or TT vs GG | 1.44 (1.15–1.80) | 0.0013 / 0.066b | -609 T increase expression in PBMC [50] | Increased TNF-α receptor 1 expression was associated with increased risk of AS. This indicates that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS. |
PTPN22
| rs2476601 | Immune response | GA or AA vs GG | 0.76 (0.58–0.98) | 0.037 / 1.00 | 1858A reduce TNF-α level in serum [51] | Reduced TNF-α level was associated with reduced risk of AS. This indicates that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS. |
IL18
| rs187238 | Cytokines | GC or CC vs GG | 0.80 (0.65–0.99) | 0.044 / 1.00 | Reduced IL-18 expression, and thus reduced IL-17 and TNF-α activity, was associated with reduced risk of AS. This indicates that a genetically determined high activity of the IL23/IL17 pathway was associated with increased risk of AS. | |
IL23R
| rs11209026 | Cytokines | GA or AA vs GG | 0.60 (0.42–0.87) | 0.0071 / 0.36 | rs11209026A reduce IL-17 level in PBMC [52] | Reduced IL-17 level was associated with reduced risk of AS. This indicates that a genetically determined high activity of the IL23/IL17 pathway was associated with increased risk of AS. |
Power calculation
Statistical analysis
Haplotype combinations | Haplotypes | NAS (%) | NControl (%) | ORa | (95% CI) | P-value | ||
---|---|---|---|---|---|---|---|---|
rs4696480 A > T | rs11938228 C > A | rs3804099 T>Cb | ||||||
11 | T:T | A:A | T:T | 69 (11) | 76 (10) | 1.00 | – | – |
22 | A:A | C:C | C:C | 72 (11) | 74 (10) | 1.07 | 0.68–1.70 | 0.82 |
33 | A:A | C:C | T:T | 28 (4) | 34 (5) | 0.91 | 0.50–1.65 | 0.76 |
44 | T:T | C:C | C:C | 14 (2) | 10 (1) | 1.52 | 0.64–3.70 | 0.38 |
12 | T:A | C:A | C:T | 158 (24) | 197 (27) | 0.88 | 0.60–1.30 | 0.55 |
13 | T:A | C:A | T:T | 76 (12) | 103 (14) | 0.81 | 0.52–1.26 | 0.37 |
14 | T:T | C:A | C:T | 59 (9) | 49 (7) | 1.33 | 0.80–2.19 | 0.31 |
23 | A:A | C:C | C:T | 77 (12) | 89 (12) | 0.95 | 0.61–1.49 | 0.91 |
24 | T:A | C:C | C:C | 52 (8) | 55 (8) | 1.04 | 0.63–1.72 | 0.90 |
34 | T:A | C:C | C:T | 51 (8) | 44 (6) | 1.28 | 0.76–2.14 | 0.43 |
Haplotype combinations | Haplotypes | NAS (%) | NControl (%) | ORa | (95% CI) | P-value | ||
---|---|---|---|---|---|---|---|---|
rs12377632 T > C | rs1554973 T > C | rs5030728 G > A | ||||||
11 | C:C | T:T | G:G | 95 (14) | 101 (14) | 1.00 | – | – |
22 | T:T | T:T | A:A | 69 (10) | 74 (10) | 0.99 | 0.64–1.53 | 1.00 |
33 | T:T | C:C | G:G | 29 (4) | 57 (8) | 0.54 | 0.32–0.92 | 0.03 |
44 | T:T | T:T | G:G | 3 (0) | 5 (1) | 0.64 | 0.15–2.74 | 0.72 |
12 | T:C | T:T | G:A | 154 (23) | 188 (25) | 0.87 | 0.61–1.24 | 0.47 |
13 | T:C | T:C | G:G | 126 (19) | 129 (17) | 1.04 | 0.72–1.51 | 0.85 |
14 | T:C | T:T | G:G | 30 (5) | 32 (4) | 1.00 | 0.56–1.77 | 1.00 |
23 | T:T | T:C | G:A | 99 (15) | 106 (14) | 0.99 | 0.67–1.47 | 1.00 |
24 | T:T | T:T | G:A | 31 (5) | 24 (3) | 1.37 | 0.75–2.51 | 0.36 |
34 | T:T | T:C | G:G | 28 (4) | 26 (4) | 1.14 | 0.63–2.09 | 0.76 |
Haplotype combinations | Haplotypes | NAS (%) | NControl (%) | ORa | (95% CI) | P-value | ||
---|---|---|---|---|---|---|---|---|
rs4848306 | rs1143623 | rs1143627 | ||||||
11 | A:A | G:G | T:T | 125 (18) | 148 (20) | 1.00 | – | – |
22 | G:G | C:C | C:C | 52 (8) | 54 (7) | 1.14 | 0.73–1.79 | 0.65 |
33 | G:G | G:G | T:T | 32 (5) | 41 (5) | 0.92 | 0.55–1.55 | 0.79 |
44 | G:G | G:G | C:C | 5 (1) | 3 (0) | 1.97 | 0.46–8.42 | 0.48 |
12 | A:G | G:C | T:C | 163 (24) | 185 (24) | 1.04 | 0.76–1.43 | 0.81 |
13 | A:G | G:G | T:T | 141 (20) | 147 (19) | 1.14 | 0.82–1.58 | 0.50 |
14 | A:G | G:G | T:C | 44 (6) | 38 (5) | 1.37 | 0.84–2.25 | 0.26 |
23 | G:G | C:G | C:T | 84 (12) | 92 (12) | 1.08 | 0.74–1.58 | 0.70 |
24 | G:G | C:G | C:C | 28 (4) | 34 (4) | 0.98 | 0.56–1.70 | 1.00 |
34 | G:G | G:G | T:C | 14 (2) | 16 (2) | 1.04 | 0.49–2.21 | 1.00 |
Haplotype combinations | Haplotypes | NAS (%) | NControl (%) | ORa | (95% CI) | P-value | |
---|---|---|---|---|---|---|---|
rs361525 G>Ab | rs1800629 G>Ac | ||||||
11 | G:G | G:G | 523 (76) | 469 (61) | 1.00 | – | – |
22 | G:G | A:A | 9 (1) | 25 (3) | 0.32 | (0.15–0.70) | 0.005 |
12 | G:G | G:A | 125 (18) | 210 (28) | 0.53 | (0.41–0.69) | < 0.0001 |
13 | G:A | G:G | 26 (4) | 47 (6) | 0.50 | (0.30–0.81) | 0.007 |
14 | G:A | G:A | 4 (1) | 12 (2) | 0.30 | (0.10–0.93) | 0.05 |