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. 2017 Mar 7;7:44015. doi: 10.1038/srep44015

Table 3. Associations between gene polymorphisms and MTX efficacy in RA patients.

Outcome No. of Included studies Pooled OR 95% CI Z P for Z test I2 (%) Chi-squared P for Chi-squared
MTHFR C677T (rs1801133)
C vs. T (Pre-allele model)
 European 6 1.010 0.731–1.396 0.06 0.951 52 10.43 0.064
 East Asian 1 0.823 0.446–1.519 0.62 0.533 — 0.00 —
 South Asian 3 0.875 0.522–1.467 0.51 0.612 0 1.31 0.520
 Overall 10 0.969 0.768–1.222 0.26 0.792 28 12.50 0.186
CC vs. CT + TT (dominant model)
 European 6 0.947 0.736–1.289 0.18 0.854 16.7 6.01 0.306
 East Asian 1 0.649 0.242–1.741 0.86 0.390 — 0.00 —
 South Asian 3 0.900 0.505–1.605 0.36 0.721 0 1.12 0.570
 Overall 10 0.937 0.734–1.197 0.52 0.604 0 7.75 0.559
TT vs. CC + CT (recessive Model)
 European 6 0.762 0.478–1.215 1.14 0.253 49.9 9.98 0.076
 East Asian 1 1.122 0.352–3.570 0.19 0.846 — 0.00 —
 South Asian 3 1.580 0.372–6.703 0.62 0.535 0 0.90 0.638
 Overall 10 0.851 0.564–1.285 0.77 0.444 24.9 11.99 0.214
CT vs. CC + TT (codominant Model)
 European 6 1.132 0.856–1.498 0.87 0.383 0 4.60 0.467
 East Asian 1 1.304 0.545–3.121 -.60 0.551 — 0.00 —
 South Asian 3 1.034 0.566–1.889 0.11 0.915 0 0.79 0.672
 Overall 10 1.128 0.884–1.439 0.97 0.332 0 5.57 0.782
CC vs. TT (homozygotic Model)
 European 6 1.257 0.766–2.603 0.90 0.366 46.4 9.33 0.097
 East Asian 1 0.657 0.169–2.549 0.61 0.543 — 0.00 —
 South Asian 3 0.594 0.139–2.541 0.70 0.482 0 0.91 0.635
 Overall 10 1.092 0.703–1.696 0.39 0.696 22.7 11.64 0.234
MTHFR A1298C (rs1801131)
A vs. C (Pre-allele model)
 European 4 1.021 0.701–1.487 0.11 0.913 48.1 5.78 0.123
 East Asian 2 0.694 0.164–2.930 0.50 0.619 76.6 4.28 0.039
 South Asian 2 1.201 0.811–1.778 0.91 0.360 0 0.77 0.382
 Overall 8 1.004 0.749–1.346 0.03 0.979 43.9 12.49 0.086
AA vs. AC + CC (dominant model)
 European 4 1.135 0.750–1.718 0.60 0.548 20.5 3.77 0.287
 East Asian 2 0.658 0.110–3.932 0.46 0.647 73.4 3.76 0.052
 South Asian 2 0.671 0.273–1.648 0.87 0.384 21.9 1.28 0.258
 Overall 8 0.908 0.596–1.382 0.45 0.652 42.0 12.06 0.099
CC vs. AC + AA (recessive Model)
 European 4 1.238 0.564–2.720 0.53 0.595 42.9 5.25 0.154
 East Asian 2 0.824 0.186–3.648 0.26 0.799 0 0.18 0.670
 South Asian 2 0.454 0.228–0.906 2.24 0.025 0 0.45 0.504
 Overall 8 0.861 0.494–1.503 0.53 0.599 35.9 10.93 0.142
AC vs. AA + CC (codominant Model)
 European 4 0.782 0.551–1.111 1.37 0.170 0 1.09 0.780
 East Asian 2 1.707 0.424–6.876 0.75 0.452 61.7 2.61 0.106
 South Asian 2 2.319 1.317–4.086 2.91 0.004 0 0.05 0.831
 Overall 8 1.205 0.772–1.882 0.82 0.412 55.0 15.54 0.030
AA vs. CC (homozygotic Model)
 European 4 0.819 0.461–1.456 0.68 0.497 52.5 6.31 0.097
 East Asian 2 1.296 0.263–6.389 0.32 0.750 0 0.56 0.453
 South Asian 2 1.375 0.586–3.224 0.73 0.465 32.5 1.48 0.224
 Overall 8 0.987 0.626–1.554 0.06 0.954 24.4 9.25 0.235
ATIC 347C > G (rs2372536)
C vs. G (Pre-allele model)
 European 2 1.736 1.176–2.564 2.77 0.006 0 0.13 0.720
 East Asian 1 1.503 0.752–3.005 1.15 0.248 — 0.00 —
 South Asian 2 0.980 0.730–1.316 0.13 0.895 0 0.01 0.942
 Overall 5 1.263 0.958–1.666 1.65 0.098 30.3 5.74 0.220
CC vs. CG + GG (dominant model)
 European 2 2.346 1.407–3.910 3.27 0.001 0 0.20 0.654
 East Asian 1 1.474 0.632–3.436 0.90 0.369 — 0.00 —
 South Asian 2 1.187 0.734–1.921 0.70 0.485 0 0.53 0.467
 Overall 5 1.612 1.168–2.224 2.91 0.004 8.2 4.35 0.360
GG vs. CG + CC (recessive Model)
 European 2 0.770 0.309–1.918 0.56 0.575 0 0.02 0.882
 East Asian 1 0.435 0.083–2.279 0.99 0.324 — 0.00 —
 South Asian 2 1.277 0.772–2.113 0.95 0.342 0 0.57 0.451
 Overall 5 1.068 0.699–1.630 0.30 0.762 0 2.65 0.618
CG vs. CC + GG (codominant Model)
 European 2 0.458 0.274–0.764 2.99 0.003 0 0.09 0.762
 East Asian 1 0.824 0.340–1.994 0.43 0.667 — 0.00 —
 South Asian 2 0.743 0.489–1.128 1.40 0.163 33.1 1.50 0.221
 Overall 5 0.634 0.468–0.858 2.95 0.003 0.9 4.04 0.401
CC vs.GG (homozygotic Model)
 European 2 1.984 0.763–5.161 1.40 0.160 0 0.09 0.764
 East Asian 1 2.526 0.468–13.639 1.08 0.281 — 0.00 —
 South Asian 2 0.912 0.488–1.704 0.29 0.773 0 0.01 0.941
 Overall 5 1.229 0.749–2.015 0.82 0.415 0 2.69 0.611
TYMS 28-bp repeat
2R vs. 3R (Pre-allele model) 3 1.174 0.811–1.697 0.85 0.396 55.5 4.49 0.106
2R2R vs. 2R3R + 3R3R (dominant model) 3 1.238 0.794–1.929 0.94 0.347 0 0.75 0.686
3R3R vs. 2R3R + 2R2R (recessive Model) 3 0.787 0.377–1.644 0.64 0.524 72.4 7.24 0.027
2R3R vs. 2R2R + 3R3R(codominant Model) 3 1.093 0.666–1.794 0.35 0.724 50.7 4.06 0.132
2R2R vs. 3R3R (homozygotic Model) 3 1.400 0.675–2.906 0.90 0.366 49.1 3.93 0.14
MTRR66A > G (rs1801394)
A vs. G (Pre-allele model) 2 1.088 0.744–1.591 0.43 0.664 0 0.41 0.523
AA vs. AG + GG (dominant model) 2 1.165 0.668–2.031 0.54 0.590 0 0.03 0.864
GG vs. AG + AA (recessive Model) 2 0.961 0.502–1.841 0.12 0.905 0 0.83 0.362
AG vs. AA + GG (codominant Model) 2 0.897 0.531–1.516 0.40 0.686 0 0.07 0.792
AA vs. GG (homozygotic Model) 2 1.188 0.555–2.545 0.44 0.657 0 0.60 0.439
RFC-1 80G > A (rs1051266)
G vs. A (Pre-allele model)
 European 1 0.561 0.356–0.884 2.49 0.013 — 0.00 —
 East Asian 1 1.104 0.615–1.981 0.33 0.740 — 0.00 —
 South Asian 2 0.705 0.523–0.951 2.29 0.022 5.9 1.06 0.303
 Overall 4 0.716 0.545–0.941 2.39 0.017 30.0 4.29 0.232
GG vs. GA + AA (dominant model)
 European 1 0.480 0.204–1.130 1.68 0.093 — 0.00 —
 East Asian 1 1.086 0.376–3.135 0.15 0.878 — 0.00 —
 South Asian 2 0.642 0.415–0.993 1.99 0.046 34.7 1.53 0.216
 Overall 4 0.645 0.449–0.926 2.38 0.017 0 2.92 0.405
AA vs. GA + GG (recessive Model)
 European 1 2.343 1.169–4.694 2.40 0.016 — 0.00 —
 East Asian 1 0.824 0.322–2.109 0.40 0.687 — 0.00 —
 South Asian 2 1.705 0.980–2.964 1.89 0.059 0 0 0.952
 Overall 4 1.653 1.115–2.451 2.50 0.012 2.9 3.09 0.378
GA vs. GG + AA (codominant Model)
 European 1 0.785 0.418–1.476 0.75 0.453 — 0.00 —
 East Asian 1 1.102 0.481–2.525 0.23 0.818 — 0.00 —
 South Asian 2 1.113 0.742–1.668 0.52 0.606 13.2 1.15 0.283
 Overall 4 1.018 0.743–1.396 0.11 0.910 0 2.02 0.567
GG vs. AA (homozygotic Model)
 European 1 0.301 0.114–0.796 2.42 0.016 — 0.00 —
 East Asian 1 1.235 0.353–4.320 0.33 0.741 — 0.00 —
 South Asian 2 0.473 0.252–0.887 2.33 0.020 0 0.33 0.563
 Overall 4 0.488 0.302–0.789 2.93 0.003 12.1 3.41 0.332
SLC19A1 G > A (rs7499)
G vs. A (Pre-allele model) 2 1.536 1.176–2.005 3.15 0.002 0 0.02 0.893
GG vs. GA + AA (dominant model) 2 1.681 1.146–2.467 2.66 0.008 0 0.19 0.66
AA vs. GA + GG (recessive Model) 2 0.528 0.316–0.884 2.43 0.015 0 0.49 0.484
GA vs. GG + AA (codominant Model) 2 0.861 0.596–1.242 0.80 0.423 0 0.73 0.394
GG vs. AA (homozygotic Model) 2 2.397 1.359–4.229 3.02 0.003 0 0.10 0.753
SLC19A1 A > G (rs2838956)
A vs. G (Pre-allele model) 2 1.366 1.051–1.776 2.33 0.020 0 0.21 0.644
AA vs. AG + GG (dominant model) 2 1.426 0.965–2.109 1.78 0.075 8.2 1.09 0.297
GG vs. AG + AA (recessive Model) 2 0.592 0.361–0.969 2.08 0.037 0 0.09 0.764
AG vs. AA + GG (codominant Model) 2 0.980 0.635–1.512 0.09 0.927 28.6 1.40 0.237
AA vs. GG (homozygotic Model) 2 1.973 1.131–3.443 2.39 0.017 0 0.10 0.754
ABCB1 C3435T (rs1045642)
C vs. T (Pre-allele model) 2 1.714 0.65–4.522 1.09 0.276 86.9 7.63 0.006
CC vs. CT + TT (dominant model) 2 1.755 0.573–5.372 0.99 0.325 75.4 4.07 0.044
TT vs. CC + CT (recessive Model) 2 0.429 0.093–1.985 1.08 0.279 83.4 6.04 0.014
CT vs. CC + TT (codominant Model) 2 1.033 0.666–1.602 0.15 0.884 0 0.04 0.838
CC vs. TT (homozygotic Model) 2 2.973 0.401–22.016 1.07 0.286 86.6 7.48 0.006