Cytokine genotypes and haplotypes associated with increased or decreased risk of TRM in unrelated donor SCT at 12 months
Locus/haplotype and allele(s) . | Allele frequency* . | Status . | Phenotype . | No. died/total . | Cl of TRM at 12 months, % (95% Cl, %) . | P . | Cl of relapse at 12 months, % (95% Cl, %) . |
|---|---|---|---|---|---|---|---|
| Overall | NA | NA | NA | 73/182 | 40 (33-47) | NA | 12 (7-17) |
| TNFSF2-1031C | 0.2 | R | C+ | 25/46 | 54 (38-70) | .04 | 5 (0-11) |
| TNFSF2-1031C | 0.2 | R | C− | 36/111 | 32 (23-41) | 13 (7-19) | |
| TNF d4 | 0.22 | R | d4+ | 35/62 | 56 (42-70) | < .01 | 3 (0-7) |
| TNF d4 | 0.22 | R | d4− | 30/99 | 30 (21-39) | 14 (7-21) | |
| TNF d4 | 0.22 | D | d4+ | 34/65 | 52 (39-65) | .02 | 11 (4-18) |
| TNF d4 | 0.22 | D | d4− | 33/99 | 33 (24-42) | 11 (5-17) | |
| TNF a5 | 0.06 | R | a5+ | 12/17 | 71 (45-97) | < .01 | 12 (0-26) |
| TNF a5 | 0.06 | R | a5− | 57/154 | 37 (29-45) | 12 (7-17) | |
| TNF a6 | 0.16 | D | a6+ | 15/50 | 30 (17-43) | .05 | 20 (9-31) |
| TNF a6 | 0.16 | D | a6− | 54/118 | 46 (37-55) | 8 (3-13) | |
| TNF a7 | 0.05 | D | a7+ | 12/18 | 67 (42-92) | < .01 | 0 |
| TNF a7 | 0.05 | D | a7− | 57/150 | 38 (30-46) | 13 (8-18) | |
| TNF d4/TNFSF2-1031C | NA | R or D | d4+/C+ | 42/77 | 55 (43-67) | < .01 | 9 (3-15) |
| TNF d4/TNFSF2-1031C | NA | R or D | Others | 14/68 | 21 (12-30) | 12 (8-16) | |
| IL 10 R2-G-C-C | NA | D | R2-G-C-C+ | 22/36 | 61 (43-79) | .01 | 11 (1-21) |
| IL 10 R2-G-C-C | NA | D | Others | 33/97 | 34 (25-43) | 10 (4-16) | |
| IL 10 R3-G-C-C | NA | D | R3-G-C-C+ | 21/69 | 30 (19-41) | .01 | 13 (5-21) |
| IL 10 R3-G-C-C | NA | D | Others | 34/64 | 53 (40-66) | 8 (2-14) |
Locus/haplotype and allele(s) . | Allele frequency* . | Status . | Phenotype . | No. died/total . | Cl of TRM at 12 months, % (95% Cl, %) . | P . | Cl of relapse at 12 months, % (95% Cl, %) . |
|---|---|---|---|---|---|---|---|
| Overall | NA | NA | NA | 73/182 | 40 (33-47) | NA | 12 (7-17) |
| TNFSF2-1031C | 0.2 | R | C+ | 25/46 | 54 (38-70) | .04 | 5 (0-11) |
| TNFSF2-1031C | 0.2 | R | C− | 36/111 | 32 (23-41) | 13 (7-19) | |
| TNF d4 | 0.22 | R | d4+ | 35/62 | 56 (42-70) | < .01 | 3 (0-7) |
| TNF d4 | 0.22 | R | d4− | 30/99 | 30 (21-39) | 14 (7-21) | |
| TNF d4 | 0.22 | D | d4+ | 34/65 | 52 (39-65) | .02 | 11 (4-18) |
| TNF d4 | 0.22 | D | d4− | 33/99 | 33 (24-42) | 11 (5-17) | |
| TNF a5 | 0.06 | R | a5+ | 12/17 | 71 (45-97) | < .01 | 12 (0-26) |
| TNF a5 | 0.06 | R | a5− | 57/154 | 37 (29-45) | 12 (7-17) | |
| TNF a6 | 0.16 | D | a6+ | 15/50 | 30 (17-43) | .05 | 20 (9-31) |
| TNF a6 | 0.16 | D | a6− | 54/118 | 46 (37-55) | 8 (3-13) | |
| TNF a7 | 0.05 | D | a7+ | 12/18 | 67 (42-92) | < .01 | 0 |
| TNF a7 | 0.05 | D | a7− | 57/150 | 38 (30-46) | 13 (8-18) | |
| TNF d4/TNFSF2-1031C | NA | R or D | d4+/C+ | 42/77 | 55 (43-67) | < .01 | 9 (3-15) |
| TNF d4/TNFSF2-1031C | NA | R or D | Others | 14/68 | 21 (12-30) | 12 (8-16) | |
| IL 10 R2-G-C-C | NA | D | R2-G-C-C+ | 22/36 | 61 (43-79) | .01 | 11 (1-21) |
| IL 10 R2-G-C-C | NA | D | Others | 33/97 | 34 (25-43) | 10 (4-16) | |
| IL 10 R3-G-C-C | NA | D | R3-G-C-C+ | 21/69 | 30 (19-41) | .01 | 13 (5-21) |
| IL 10 R3-G-C-C | NA | D | Others | 34/64 | 53 (40-66) | 8 (2-14) |
Univariate comparisons were made to analyze associations between TNFSF2 region and IL 10 polymorphisms previously implicated as predictive of TRM. Only univariate statistically significant associations are shown in the Table. Factors that remained statistically significant in the Cox regression model included TNF d4/TNFSF2 -1031C and TNFa5.
NA indicates not applicable; R, recipient; and D, donor.
Allele frequencies were all in Hardy-Weinberg equilibrium. IL 10 haplotypes were determined by physical linkage.19