Table 2.
Gene–gene interactions of studied oxidative stress-related polymorphisms and MS risk.
| Combined genotype | Control (n = 140) | MS (n = 142) | Crude OR (95% CI)* | p* | Adjusted OR (95% CI)** | p** | ||
|---|---|---|---|---|---|---|---|---|
| Number | Frequency | Number | Frequency | |||||
| c.47 C > T (p.Val16Ala)—SOD2 (rs4880) AND c.-89 A > T—CAT (rs7943316) | ||||||||
| T/T–A/A | 4 | 0.029 | 4 | 0.028 | 0.986 (0.242–4.020) | 0.999 | 1.005 (0.244–0.135) | 0.999 |
| T/T–A/T | 23 | 0.164 | 30 | 0.211 | 1.363 (0.746–2.487) | 0.529 | 1.504 (0.814–2.778) | 0.349 |
| T/T–T/T | 1 | 0.007 | 2 | 0.014 | 1.986 (0.178–22.151) | 0.821 | 1.790 (0.158–20.259) | 0.869 |
| T/C–A/A | 15 | 0.107 | 9 | 0.063 | 0.564 (0.238–1.335) | 0.349 | 0.572 (0.241–1.361) | 0.371 |
| T/C–A/T | 51 | 0.364 | 68 | 0.479 | 1.604 (0.996–2.582) | 0.101 | 1.571 (0.973–2.536) | 0.126 |
| T/C–T/T | 8 | 0.057 | 6 | 0.042 | 0.728 (0.246–2.155) | 0.812 | 0.746 (0.251–2.223) | 0.839 |
| C/C–A/A | 5 | 0.036 | 0 | 0.000 | 0.000 (0.000–+ ∞) | 0.999 | 0.000 (0.000–+ ∞) | 0.999 |
| C/C–A/T | 23 | 0.164 | 20 | 0.141 | 0.834 (0.435–1.599) | 0.827 | 0.791 (0.410–1.526) | 0.734 |
| C/C–T/T | 10 | 0.071 | 3 | 0.021 | 0.281 (0.076–1.042) | 0.113 | 0.249 (0.066–0.936) | 0.078 |
| c.47 C > T (p.Val16Ala)—SOD2 (rs4880) AND c.660 T > C—GPX4 (rs713041) | ||||||||
| T/T–T/T | 3 | 0.021 | 5 | 0.035 | 1.667 (0.391–7.111) | 0.740 | 1.710 (0.398–7.358) | 0.720 |
| T/T–T/C | 14 | 0.100 | 19 | 0.134 | 1.390 (0.668–2.896) | 0.614 | 1.510 (90.718–3.174) | 0.2477 |
| T/T–C/C | 11 | 0.079 | 12 | 0.085 | 1.083 (0.461–2.542) | 0.979 | 1.146 (0.485–2.709) | 0.940 |
| T/C–T/T | 12 | 0.086 | 23 | 0.162 | 2.062 (0.982–4.326) | 0.109 | 1.959 (0.929–4.133) | 0.148 |
| T/C–T/C | 34 | 0.243 | 43 | 0.303 | 1.354 (0.800–2.293) | 0.451 | 1.384 (0.814–2.353) | 0.407 |
| T/C–C/C | 28 | 0.200 | 17 | 0.120 | 0.544 (0.283–1.047) | 0.131 | 0.539 (0.279–1.041) | 0.128 |
| C/C–T/T | 3 | 0.021 | 3 | 0.021 | 0.986 (0.196–4.968) | 0.999 | 1.025 (0.201–5.213) | 0.999 |
| C/C–T/C | 17 | 0.121 | 10 | 0.070 | 0.548 (0.242–1.243) | 0.278 | 0.505 (0.220–1.157) | 0.201 |
| C/C–C/C | 18 | 0.129 | 10 | 0.070 | 0.513 (0.228–1.156) | 0.203 | 0.487 (0.215–1.105) | 0.163 |
| c.47 C > T (p.Val16Ala)—SOD2 (rs4880) AND g.117803515 C > T—NOS1 (rs1879417) | ||||||||
| T/T–C/C | 6 | 0.043 | 13 | 0.092 | 2.251 (0.830–6.100) | 0.210 | 2.462 (0.900–6.738) | 0.152 |
| T/T–C/T | 11 | 0.079 | 15 | 0.106 | 1.385 (0.613–3.131) | 0.680 | 1.387 (0.611–3.151) | 0.680 |
| T/T–T/T | 11 | 0.079 | 8 | 0.056 | 0.700 (0.273–1.796) | 0.706 | 0.787 (0.303–2.044) | 0.858 |
| T/C–C/C | 12 | 0.086 | 16 | 0.113 | 1.354 (0.616–2.978) | 0.698 | 1.485 (0.669–3.298) | 0.552 |
| T/C–C/T | 44 | 0.314 | 43 | 0.303 | 0.948 (0.572–1.571) | 0.973 | 0.929 (0.558–1.545) | 0.950 |
| T/C–T/T | 18 | 0.129 | 24 | 0.169 | 1.379 (0.711–2.671) | 0.566 | 1.312 (0.673–2.556) | 0.669 |
| C/C–C/C | 5 | 0.036 | 6 | 0.042 | 1.191 (0.355–3.996) | 0.950 | 1.034 (0.303–3.524) | 0.998 |
| C/C–C/T | 23 | 0.164 | 12 | 0.085 | 0.470 (0.224–0.985) | 0.090 | 0.470 (0.223–0.990) | 0.092 |
| C/C–T/T | 10 | 0.071 | 5 | 0.035 | 0.474 (0.158–1.425) | 0.334 | 0.428 (0.141–1.302) | 0.252 |
| c.47 C > T (p.Val16Ala)—SOD2 (rs4880) AND c.1823 C > T (p.Ser608Leu)—NOS2 (rs2297518) | ||||||||
| T/T–C/C | 14 | 0.100 | 17 | 0.120 | 1.224 (0.579–2.590) | 0.838 | 1.311 (0.615–2.796) | 0.733 |
| T/T–C/T | 10 | 0.071 | 8 | 0.056 | 0.776 (0.297–2.028) | 0.844 | 0.806 (0.307–2.118) | 0.885 |
| T/T–T/T | 4 | 0.029 | 11 | 0.077 | 2.855 (0.887–9.192) | 0.152 | 3.120 (0.960–10.136) | 0.113 |
| T/C–C/C | 37 | 0.264 | 67 | 0.472 | 2.487 (1.509–4.099) | 0.0020.951 | 2.471 (1.495–4.084) | 0.0020.949 |
| T/C–C/T | 21 | 0.150 | 13 | 0.092 | 0.571 (0.274–1.191) | 0.252 | 0.569 (0.272–1.192) | 0.252 |
| T/C–T/T | 16 | 0.114 | 3 | 0.021 | 0.167 (0.048–0.588) | 0.0100.853 | 0.164 (0.046–0.579) | 0.0100.856 |
| C/C–C/C | 9 | 0.064 | 15 | 0.106 | 1.719 (0.726–4.069) | 0.388 | 1.697 (0.713–4.037) | 0.410 |
| C/C–C/T | 17 | 0.121 | 8 | 0.056 | 0.432 (0.180–1.036) | 0.116 | 0.414 (0.171–1.000) | 0.098 |
| C/C–T/T | 12 | 0.086 | 0 | 0.000 | 0.000 (0.000–+ ∞) | 0.999 | 0.000 (0.000–+ ∞) | 0.999 |
| c.660 T > C—GPX4 (rs713041) AND c.-89 A > T—CAT (rs7943316) | ||||||||
| T/T–A/A | 4 | 0.029 | 2 | 0.014 | 0.486 (0.088–2.695) | 0.651 | 0.646 (0.083–2.600) | 0.618 |
| T/T–A/T | 13 | 0.093 | 26 | 0.183 | 2.190 (1.075–4.462) | 0.061 | 2.109 (1.031–4.316) | 0.080 |
| T/T–T/T | 1 | 0.007 | 3 | 0.021 | 3.000 (0.308–29.194) | 0.570 | 3.274 (0.333–32.173) | 0.523 |
| T/C–A/A | 13 | 0.093 | 9 | 0.063 | 0.661 (0.273–1.600) | 0.589 | 0.705 (0.289–1.718) | 0.689 |
| T/C–A/T | 43 | 0.307 | 57 | 0.401 | 1.513 (0.925–2.473) | 0.188 | 1.530 (0.933–2.509) | 0.176 |
| T/C–T/T | 9 | 0.064 | 6 | 0.042 | 0.642 (0.222–1.854) | 0.655 | 0.624 (0.215–1.815) | 0.624 |
| C/C–A/A | 7 | 0.050 | 2 | 0.014 | 0.271 (0.055–1.330) | 0.204 | 0.264 (0.054–1.305) | 0.194 |
| C/C–A/T | 41 | 0.293 | 35 | 0.246 | 0.790 (0.66–1.338) | 0.617 | 0.805 (0.474–1.369) | 0.688 |
| C/C–T/T | 9 | 0.064 | 2 | 0.014 | 0.208 (0.044–0.980) | 0.092 | 0.182 (0.038–0.868) | 0.065 |
| c.660 T > C—GPX4 (rs713041) AND g.117803515 C > T—NOS1 (rs1879417) | ||||||||
| T/T–C/C | 4 | 0.029 | 6 | 0.042 | 1.500 (0.414–5.434) | 0.786 | 1.593 (0.436–5.819) | 0.731 |
| T/T–C/T | 8 | 0.057 | 19 | 0.134 | 2.549 (1.077–6.034) | 0.065 | 1.418 (1.016–5.754) | 0.090 |
| T/T–T/T | 6 | 0.043 | 6 | 0.042 | 0.985 (0.310–3.132) | 0.999 | 0.948 (0.296–3.038) | 0.995 |
| T/C–C/C | 17 | 0.121 | 19 | 0.134 | 1.118 (0.555–2.252) | 0.940 | 1.136 (0.562–2.299) | 0.923 |
| T/C–C/T | 32 | 0.229 | 32 | 0.225 | 0.982 (0.562–1.714) | 0.997 | 0.998 (0.569–1.748) | 0.999 |
| T/C–T/T | 16 | 0.114 | 21 | 0.148 | 1.345 (90.670–2.700) | 0.646 | 1.359 (0.674–2.740) | 0.629 |
| C/C–C/C | 2 | 0.014 | 10 | 0.070 | 5.227 (1.124–24.306) | 0.069 | 5.791 (1.235–27.156) | 0.051 |
| C/C–C/T | 38 | 0.271 | 19 | 0.134 | 0.415 (0.225–0.763) | 0.0100.816 | 0.409 (0.222–0.757) | 0.0100.826 |
| C/C–T/T | 17 | 0.121 | 10 | 0.070 | 0.548 (0.242–1.243) | 0.278 | 0.526 (0.231–1.202) | 0.240 |
| c.660 T > C—GPX4 (rs713041) AND c.1823 C > T (p.Ser608Leu)—NOS2 (rs2297518) | ||||||||
| T/T–C/C | 7 | 0.050 | 24 | 0.169 | 3.864 (1.607–9.295) | 0.0060.888 | 3.648 (1.509–8.818) | 0.0080.851 |
| T/T–C/T | 11 | 0.079 | 3 | 0.021 | 0.253 (0.069–0.928) | 0.075 | 0.248 (0.067–0.915) | 0.071 |
| T/T–T/T | 0 | 0.000 | 4 | 0.028 | 4,062,394.411 (0.000–+ ∞) | 0.999 | 5,019,550,116 (0.000–+ ∞) | 0.999 |
| T/C–C/C | 32 | 0.229 | 52 | 0.366 | 1.950 (1.157–3.286) | 0.0240.713 | 2.081 (1.225–3.538) | 0.0140.795 |
| T/C–C/T | 15 | 0.107 | 15 | 0.106 | 0.984 (0.462–2.098) | 0.999 | 0.993 (0.464–2.127) | 0.999 |
| T/C–T/T | 18 | 0.129 | 5 | 0.035 | 0.247 (0.089–0.686) | 0.0240.800 | 0.222 (0.079–0.625) | 0.0140.835 |
| C/C–C/C | 21 | 0.150 | 23 | 0.162 | 1.095 (0.575–2.085) | 0952 | 1.089 (0.570–2.081) | 0.959 |
| C/C–C/T | 22 | 0.157 | 11 | 0.077 | 0.450 (0.210–0.968) | 0.080 | 0.445 (0.206–0.960) | 0.076 |
| C/C–T/T | 14 | 0.100 | 5 | 0.035 | 0.328 (0.115–0.938) | 0.075 | 0.332 (0.116–0.954) | 0.080 |
| g.117803515 C > T—NOS1 (rs1879417) AND c.-89 A > T—CAT (rs7943316) | ||||||||
| C/C–A/A | 8 | 0.057 | 4 | 0.028 | 0.478 (0.141–1.626) | 0.418 | 0.493 (0.144–1.688) | 0.452 |
| C/C–A/T | 15 | 0.107 | 29 | 0.204 | 2.139 (1.091–4.193) | 0.053 | 2.261 (1.145–4.465) | 0.0380.673 |
| C/C–T/T | 0 | 0.000 | 2 | 0.014 | 4,004,360,205 (0.000–+ ∞) | 0.999 | 3,909,419.356 (0.000–+ ∞) | 0.999 |
| C/T–A/A | 8 | 0.057 | 5 | 0.035 | 0.602 (0.192–1.888) | 0.621 | 0.586 (0.186–1.852) | 0.594 |
| C/T–A/T | 58 | 0.414 | 60 | 0.423 | 1.034 (0.644–1.661) | 0.987 | 1.017 (0.632–1.638) | 0.997 |
| C/T–T/T | 12 | 0.086 | 5 | 0.035 | 0.389 (0.133–1.136) | 0.161 | 0.397 (0.136–1.165) | 0.177 |
| T/T–A/A | 8 | 0.057 | 4 | 0.028 | 0.478 (0.141–1.626) | 0.418 | 0.512 (0.150–1.755) | 0.492 |
| T/T–A/T | 24 | 0.171 | 29 | 0.204 | 1.240 (0.681–2.259) | 0.731 | 1.233 (0.675–2.254) | 0.746 |
| T/T–T/T | 7 | 0.050 | 4 | 0.028 | 0.551 (0.158–1.925) | 0.578 | 0.468 (0.133–1.665) | 0.424 |
| g.117803515 C > T—NOS1 (rs1879417) AND c.1823 C > T (p.Ser608Leu)—NOS2 (rs2297518) | ||||||||
| C/C–C/C | 17 | 0.121 | 20 | 0.141 | 1.186 (0.593–2.373) | 0.862 | 1.249 (0.620–2.514) | 0.782 |
| C/C–C/T | 5 | 0.036 | 8 | 0.056 | 1.612 (0.514–5.053) | 0.655 | 1.534 (0.486–4.845) | 0.715 |
| C/C–T/T | 1 | 0.007 | 7 | 0.049 | 7.207 (0.875–59.367) | 0.128 | 8.481 (1.021–70.485) | 0.094 |
| C/T–C/C | 35 | 0.250 | 57 | 0.401 | 2.012 (1.209–3.346) | 0.0140.773 | 1.992 (1.194–2.323) | 0.0160.760 |
| C/T–C/T | 24 | 0.171 | 9 | 0.063 | 0.327 (0.146–0.732) | 0.0140.795 | 0.332 (0.148–0.746) | 0.0160.786 |
| C/T–T/T | 19 | 0.136 | 4 | 0.028 | 0.185 (0.061–0.558) | 0.0060.899 | 0.175 (0.057–0.532) | 0.0040.909 |
| T/T–C/C | 8 | 0.057 | 22 | 0.155 | 3.025 (1.298–7.050) | 0.0200.746 | 3.040 (1.299–7.116) | 0.0200.844 |
| T/T–C/T | 19 | 0.136 | 12 | 0.085 | 0.588 (0.274–1.262) | 0.316 | 0.584 (0.271–1.259) | 0.311 |
| T/T–T/T | 12 | 0.086 | 3 | 0.021 | 0.230 (0.064–0.834) | 0.0490.629 | 0.213 (0.059–0.779) | 0.0380.653 |
| c.1823 C > T (p.Ser608Leu)—NOS2 (rs2297518) AND c.-89 A > T—CAT (rs7943316) | ||||||||
| C/C–A/A | 14 | 0.100 | 7 | 0.049 | 0.467 (0.182–1.194) | 0.211 | 0.471 (0.183–1.211) | 0.222 |
| C/C–A/T | 46 | 0.329 | 82 | 0.577 | 2.793 (1.719–4.536) | 0.0020.988 | 2.844 (1.743–4.639) | 0.0020.990 |
| C/C–T/T | 0 | 0.000 | 0 | 0.000 | 0.000 (0.000–+ ∞) | 0.999 | 0.000 (0.000–+ ∞) | 0.999 |
| C/T–A/A | 7 | 0.050 | 4 | 0.028 | 0.551 (0.158–1.925) | 0.578 | 0.585 (0.166–2.059) | 0.645 |
| C/T–A/T | 31 | 0.221 | 24 | 0.169 | 0.715 (0.395–1.294) | 0.464 | 0.698 (0.384–1.268) | 0.418 |
| C/T–T/T | 10 | 0.071 | 1 | 0.007 | 0.092 (0.012–0.730) | 0.0470.667 | 0.093 (0.012–0.737) | 0.0490.667 |
| T/T–A/A | 3 | 0.021 | 2 | 0.014 | 0.652 (0.107–3.965) | 0873 | 0.655 (0.107–4.020) | 0.875 |
| T/T–A/T | 20 | 0.143 | 12 | 0.085 | 0.554 (0.260–1.181) | 0.236 | 0.562 (0.262–1.204) | 0.257 |
| T/T–T/T | 9 | 0.064 | 0 | 0.000 | 0.000 (0.000–+ ∞) | 0.999 | 0.000 (0.000–+ ∞) | 0.999 |
p < 0.05 along with corresponding ORs are bold and in bold (for the genotypes/alleles contributing to the MS development) or in italics (for the genotypes/alleles with a protective effect); *denotes p-values with the Bonferroni correction; **OR adjusted for gender. Statistical power (1 − β) for significant comparisons is given in superscripts.