Table 7.
Association of KIR loci and HLA ligands with Multiple Sclerosis
| A. Association of HLA Ligand and KIR Loci with Multiple Sclerosis | ||||||
|---|---|---|---|---|---|---|
| Molecule | Genotype | Controls (N) | Cases (N) | OR | p-value | Significance |
| HLA Ligands | C1C1 | 153 (0.365) | 164 (0.398) | 1.15 | 3.29E−01 | NS |
| HLA Ligands | C1C2 | 201 (0.480) | 200 (0.485) | 1.02 | 8.69E−01 | NS |
| HLA Ligands | C2C2 | 65 (0.155) | 47 (0.114) | 0.70 | 8.30E−02 | NS |
| HLA Ligands | Bw4+ | 263 (0.628) | 210 (0.510) | 0.62 | 5.95E−04 | * |
| HLA Ligands | Bw4Bw4 | 55 (0.131) | 36 (0.087) | 0.63 | 4.30E−02 | * |
| HLA Ligands | Bw4Bw6 | 208 (0.496) | 174 (0.422) | 0.74 | 3.20E−02 | * |
| HLA Ligands | Bw6Bw6 | 156 (0.372) | 201 (0.488) | 1.61 | 7.67E−04 | * |
| HLA Ligands | Bw6+ | 364 (0.869) | 375 (0.910) | 1.53 | 5.70E−02 | NS |
| KIR | KIR2DL2 | 206 (0.492) | 206 (0.500) | 1.03 | 8.10E−01 | NS |
| KIR | KIR2DL3 | 386 (0.921) | 369 (0.896) | 0.73 | 2.00E−01 | NS |
| KIR | KIR3DL1 | 397 (0.947) | 391 (0.949) | 1.03 | 9.20E−01 | NS |
| KIR | KIR3DS1 | 182 (0.434) | 173 (0.420) | 0.94 | 6.73E−01 | NS |
| KIR | KIR2DL2/2 | 33 (0.079) | 43 (0.104) | 1.36 | 2.00E−01 | NS |
| KIR | KIR2DL2/3 | 173 (0.413) | 163 (0.396) | 0.93 | 6.12E−01 | NS |
| KIR | KIR2DL3/3 | 213 (0.508) | 206 (0.500) | 0.97 | 8.10E−01 | NS |
| KIR | KIR3DL1/L1 | 237 (0.566) | 238 (0.578) | 1.05 | 7.26E−01 | NS |
| KIR | KIR3DL1/S1 | 160 (0.382) | 153 (0.371) | 0.96 | 7.55E−01 | NS |
| KIR | KIR3DS1/S1 | 22 (0.053) | 20 (0.049) | 0.92 | 7.94E−01 | NS |
| B. Association of HLA Ligand and KIR Loci with Multiple Sclerosis in the absence of DRB1*15:01. | ||||||
|---|---|---|---|---|---|---|
| Molecule | Genotype | Controls (N) | Cases (N) | OR | p-value | Significance |
| HLA Ligands | C1C1 | 113 (0.335) | 54 (0.286) | 0.79 | 2.41E−01 | NS |
| HLA Ligands | C1C2 | 167 (0.496) | 101 (0.534) | 1.17 | 3.93E−01 | NS |
| HLA Ligands | C2C2 | 57 (0.169) | 33 (0.175) | 1.04 | 8.73E−01 | NS |
| HLA Ligands | Bw4+ | 222 (0.659) | 110 (0.582) | 0.72 | 8.00E−02 | NS |
| HLA Ligands | Bw4Bw4 | 51 (0.151) | 20 (0.106) | 0.66 | 1.43E−01 | NS |
| HLA Ligands | Bw4Bw6 | 171 (0.507) | 90 (0.476) | 0.88 | 0.492 | NS |
| HLA Ligands | Bw6Bw6 | 115 (0.341) | 78 (0.413) | 1.36 | 0.103 | NS |
| HLA Ligands | Bw6+ | 286 (0.849) | 168 (0.889) | 1.43 | 0.198 | NS |
| KIR | KIR2DL2 | 173 (0.513) | 98 (0.519) | 1.02 | 9.09E−01 | NS |
| KIR | KIR2DL3 | 311 (0.923) | 167 (0.884) | 0.63 | 1.34E−01 | NS |
| KIR | KIR3DL1 | 319 (0.947) | 180 (0.952) | 1.13 | 7.73E−01 | NS |
| KIR | KIR3DS1 | 148 (0.439) | 69 (0.365) | 0.73 | 9.77E−02 | NS |
| KIR | KIR2DL2/2 | 26 (0.077) | 22 (0.116) | 1.58 | 1.34E−01 | NS |
| KIR | KIR2DL2/3 | 147 (0.436) | 76 (0.402) | 0.87 | 4.48E−01 | NS |
| KIR | KIR2DL3/3 | 164 (0.487) | 91 (0.481) | 0.98 | 9.09E−01 | NS |
| KIR | KIR3DL1/L1 | 189 (0.561) | 120 (0.635) | 1.36 | 0.0977 | NS |
| KIR | KIR3DL1/S1 | 130 (0.386) | 60 (0.317) | 0.74 | 0.1177 | NS |
| KIR | KIR3DS1/S1 | 18 (0.053) | 9 (0.048) | 0.89 | 0.7727 | NS |
| C. Association of Bw Motif Subgroups with Multiple Sclerosis in the Presence and Absence of DRB1*15:01. | ||||||||
|---|---|---|---|---|---|---|---|---|
| Stratum | HLA-B Position 80 Sequence | Control (N) | Case (N) | OR | 95% CI Lower | 95% CI Upper | p-value | Significance 1 |
| DRB1*15:01 Negative | T | 161 (0.239) | 68 (0.182) | 0.71 | 0.51 | 0.98 | 3.23E−02 | NS |
| N | 401 (0.595) | 244 (0.652) | 1.28 | 0.97 | 1.68 | 6.70E−02 | NS | |
| I | 112 (0.166) | 62 (0.166) | 1.00 | 0.70 | 1.42 | 9.87E−01 | NS | |
| DRB1*15:01 Positive | T | 29 (0.177) | 61 (0.137) | 0.74 | 0.45 | 1.24 | 2.16E−01 | NS |
| N | 119 (0.726) | 330 (0.740) | 1.08 | 0.70 | 1.64 | 7.22E−01 | NS | |
| I | 16 (0.098) | 55 (0.123) | 1.3 | 0.71 | 2.51 | 3.79E−01 | NS | |
Frequencies are shown in parentheses in the Controls and Cases columns.
Bw4: HLA-B alleles encoding either Threonine at codon 80 (80T) or Isoleucine at codon 80 (80I).
Bw6: HLA-B alleles encoding Asparagine at codon 80 (80N).
1
For each stratum, the evaluation of significance was informed by the significance of overall heterogeneity between cases and controls in that stratum. The p-value of locus-level heterogeneity is 8.75E−02 in the DRB1*15:01-negative stratum, and 3.64E−01 in the DRB1*15:01-positive stratum. For each stratum, the threshold of significance was calculated as 0.05/3 (1.67E−02). Significant p-values are indicated with asterisks. NS: Not Significant.