Pairwise analyses of inhibitor risk
| . | Race* . | INH(−) . | INH(+)† . | Odds . | OR‡ . | 95% CI . | P . |
|---|---|---|---|---|---|---|---|
| Viel et al,14 76 AA subjects, HA all severities | |||||||
| H3 + H4 | AA | 10 | 9 | 0.9 | 3.4 | 1.1-10.2 | .03 |
| H1 + H2 | AA | 45 | 12 | 0.3 | |||
| 173 haplotyped AA subjects | |||||||
| H3 + H4 + H5 | AA | 20 | 11 | 0.6 | 1.0 | 0.5-2.4 | 1.0 |
| H1 + H2 | AA | 93 | 49 | 0.5 | |||
| 362 haplotyped AA + W subjects§ | |||||||
| H3 + H4 + H5 | AA + W | 21 | 11 | 0.5 | 1.2 | 0.6-2.6 | .7 |
| H1 + H2 | AA + W | 231 | 99 | 0.4 | |||
| All AA subjects | 113 | 60 | 0.5 | 1.5 | 0.9-2.3 | .1 | |
| All W subjects | 139 | 50 | 0.4 | ||||
| 1241 E | AA + W | 98 | 48 | 0.5 | 1.2 | 0.8-1.9 | .4 |
| 1241 D | AA + W | 154 | 62 | 0.4 | |||
| 2238 V | AA + W | 21 | 10 | 0.5 | 1.1 | 0.5-2.4 | .8 |
| 2238 M | AA + W | 231 | 100 | 0.4 | |||
| Intron-22 inversion (+) | AA + W | 99 | 50 | 0.5 | 1.4 | 0.9-2.3 | .2 |
| Intron-22 inversion (−) | AA + W | 125 | 45 | 0.4 | |||
| Intron-22 inversion (+) | AA | 31 | 26 | 0.8 | 2.4 | 1.2-4.8 | .02 |
| Intron-22 inversion (+) | W | 68 | 24 | 0.4 | |||
| Intron-22 inversion (−) | AA | 59 | 26 | 0.4 | 1.5 | 0.8-3.0 | .3 |
| Intron-22 inversion (−) | W | 66 | 19 | 0.3 | |||
| Intron-22 inversion (+) | AA | 31 | 26 | 0.8 | 1.9 | 0.9-3.8 | .08 |
| Intron-22 inversion (−) | AA | 59 | 26 | 0.4 | |||
| Intron-22 inversion (+) | W | 68 | 24 | 0.4 | 1.2 | 0.6-2.4 | .6 |
| Intron-22 inversion (−) | W | 66 | 19 | 0.3 | |||
| Intron-22 inversion (+), 1241 E | AA | 20 | 18 | 0.9 | 1.2 | 0.4-3.8 | .8 |
| Intron-22 inversion (+), 1241 D | AA | 11 | 8 | 0.7 | |||
| Intron-22 inversion (+), 2238 V | AA | 4 | 5 | 1.3 | 1.6 | 0.4-6.7 | .7 |
| Intron-22 inversion (+), 2238 M | AA | 27 | 21 | 0.8 | |||
| Intron-22 inversion (+), age 18+ y | AA | 16 | 19 | 1.2 | 2.5 | 0.8-7.7 | .1 |
| Intron-22 inversion (+), age <18 y | AA | 15 | 7 | 0.5 | |||
| Age 18+ y | AA | 59 | 39 | 0.7 | 1.7 | 0.9-3.2 | .1 |
| Age <18 y | AA | 54 | 21 | 0.4 | |||
| HLA-DR15 (H2) | AA + W | 10 | 13 | 1.3 | 1.9 | 0.7-5.0 | .3 |
| HLA-DR15 (H1) | AA + W | 30 | 21 | 0.7 | |||
| HLA-DR15 | AA | 22 | 18 | 0.8 | 1.0 | 0.4-2.3 | 1.0 |
| HLA-DR15 | W | 21 | 18 | 0.9 |
| . | Race* . | INH(−) . | INH(+)† . | Odds . | OR‡ . | 95% CI . | P . |
|---|---|---|---|---|---|---|---|
| Viel et al,14 76 AA subjects, HA all severities | |||||||
| H3 + H4 | AA | 10 | 9 | 0.9 | 3.4 | 1.1-10.2 | .03 |
| H1 + H2 | AA | 45 | 12 | 0.3 | |||
| 173 haplotyped AA subjects | |||||||
| H3 + H4 + H5 | AA | 20 | 11 | 0.6 | 1.0 | 0.5-2.4 | 1.0 |
| H1 + H2 | AA | 93 | 49 | 0.5 | |||
| 362 haplotyped AA + W subjects§ | |||||||
| H3 + H4 + H5 | AA + W | 21 | 11 | 0.5 | 1.2 | 0.6-2.6 | .7 |
| H1 + H2 | AA + W | 231 | 99 | 0.4 | |||
| All AA subjects | 113 | 60 | 0.5 | 1.5 | 0.9-2.3 | .1 | |
| All W subjects | 139 | 50 | 0.4 | ||||
| 1241 E | AA + W | 98 | 48 | 0.5 | 1.2 | 0.8-1.9 | .4 |
| 1241 D | AA + W | 154 | 62 | 0.4 | |||
| 2238 V | AA + W | 21 | 10 | 0.5 | 1.1 | 0.5-2.4 | .8 |
| 2238 M | AA + W | 231 | 100 | 0.4 | |||
| Intron-22 inversion (+) | AA + W | 99 | 50 | 0.5 | 1.4 | 0.9-2.3 | .2 |
| Intron-22 inversion (−) | AA + W | 125 | 45 | 0.4 | |||
| Intron-22 inversion (+) | AA | 31 | 26 | 0.8 | 2.4 | 1.2-4.8 | .02 |
| Intron-22 inversion (+) | W | 68 | 24 | 0.4 | |||
| Intron-22 inversion (−) | AA | 59 | 26 | 0.4 | 1.5 | 0.8-3.0 | .3 |
| Intron-22 inversion (−) | W | 66 | 19 | 0.3 | |||
| Intron-22 inversion (+) | AA | 31 | 26 | 0.8 | 1.9 | 0.9-3.8 | .08 |
| Intron-22 inversion (−) | AA | 59 | 26 | 0.4 | |||
| Intron-22 inversion (+) | W | 68 | 24 | 0.4 | 1.2 | 0.6-2.4 | .6 |
| Intron-22 inversion (−) | W | 66 | 19 | 0.3 | |||
| Intron-22 inversion (+), 1241 E | AA | 20 | 18 | 0.9 | 1.2 | 0.4-3.8 | .8 |
| Intron-22 inversion (+), 1241 D | AA | 11 | 8 | 0.7 | |||
| Intron-22 inversion (+), 2238 V | AA | 4 | 5 | 1.3 | 1.6 | 0.4-6.7 | .7 |
| Intron-22 inversion (+), 2238 M | AA | 27 | 21 | 0.8 | |||
| Intron-22 inversion (+), age 18+ y | AA | 16 | 19 | 1.2 | 2.5 | 0.8-7.7 | .1 |
| Intron-22 inversion (+), age <18 y | AA | 15 | 7 | 0.5 | |||
| Age 18+ y | AA | 59 | 39 | 0.7 | 1.7 | 0.9-3.2 | .1 |
| Age <18 y | AA | 54 | 21 | 0.4 | |||
| HLA-DR15 (H2) | AA + W | 10 | 13 | 1.3 | 1.9 | 0.7-5.0 | .3 |
| HLA-DR15 (H1) | AA + W | 30 | 21 | 0.7 | |||
| HLA-DR15 | AA | 22 | 18 | 0.8 | 1.0 | 0.4-2.3 | 1.0 |
| HLA-DR15 | W | 21 | 18 | 0.9 |
The study cohort consisted of all severe HA subjects plus 7 intron-22 inversion subjects with reported mild or moderate severity HA. These 7 subjects were included because, given the fact that intact FVIII protein cannot be translated from mRNA of inversion mutation patients, their clotting activity was presumably due to other coagulation factors besides FVIII. Therefore, it would not be expected to influence anti-FVIII immune responses. All of the pairwise comparisons of individual F8 haplotypes, and all possible subgroupings of these haplotypes, were evaluated for African American (AA), white (W), and AA + W racial groups (not shown). None of these comparisons showed a statistically significant association of F8 haplotype with inhibitor risk.
Relative risks of developing an inhibitor were evaluated for the indicated subgroups of AA and W HA subjects.
Positive inhibitor status (INH(+)) indicates the clinical record for this subject showed he had at least 1 measured inhibitor titer of ≥0.6 BU/mL.
ORs and probabilities were determined using the calculator at http://vassarstats.net/odds2x2.html to determine Fisher exact 2-way probabilities. P values <.05 were considered significant.
Haplotypes could not be assigned to 10 of the 372 subjects due to lack of DNA or poorly resolved sequence data.