Characteristics of 922 β-thalassemia patients in cohort C
| Patient characteristics . | Disease severity . | P* . | HWP† . | |
|---|---|---|---|---|
| TM (n = 568) . | TI (n = 354) . | |||
| Gender, n | 373:195 | 217:137 | .179 | |
| Males: Females | ||||
| Age (years), mean ± SD | 6.47 ± 4.24 | 11.81 ± 9.15 | <.001 | |
| Hematological data, mean ± SD | ||||
| Hemoglobin (g/L)‡ | 64.68 ± 17.88 | 71.32 ± 16.93 | <.001 | |
| HbF (g/L)§ | 9.93 ± 9.34 | 25.52 ± 19.09 | <.001 | |
| Requirement for systematic transfusion, n (%) | 568 (100.0) | 132 (37.3) | <.001 | |
| Age at first transfusion (months), median (5th-95th percentile) | 6.0 (2-24) | 24.0 (3-144)|| | <.001 | |
| HBB genotype categories, n (%)¶ | ||||
| β+/β+ | 0 (0.0) | 8 (2.3) | ||
| β+/β0 | 95 (16.7) | 197 (55.6) | ||
| β0/β0 | 473 (83.3) | 149 (42.1) | ||
| HBA genotype categories, n (%)# | ||||
| αα/αα | 508 (89.3) | 271 (76.6) | ||
| –α/αα | 28 (4.9) | 29 (8.2) | ||
| ααT/αα | 5 (0.9) | 9 (2.5) | ||
| —/αα | 27 (4.8) | 40 (11.3) | ||
| –α/αTα | 0 (0.0) | 1 (0.3) | ||
| —/–α | 0 (0.0) | 1 (0.3) | ||
| —/αTα | 0 (0.0) | 3 (0.8) | ||
| BCL11A | ||||
| rs11886868, n (%) | 0.543 | |||
| T/T | 0 (0.0) | 0 (0.0) | ||
| T/C | 29 (5.1) | 8 (2.3) | ||
| C/C | 539 (94.9) | 346 (97.7) | ||
| rs766432, n (%) | 0.646 | |||
| A/A | 345 (60.7) | 166 (49.6) | ||
| A/C | 192 (33.8) | 163 (46.0) | ||
| C/C | 31 (5.5) | 25 (7.1) | ||
| HBS1L-MYB intergenic region | ||||
| rs9399137, n (%) | 0.627 | |||
| T/T | 398 (70.1) | 220 (62.1) | ||
| T/C | 155 (27.3) | 116 (32.8) | ||
| C/C | 15 (2.6) | 18 (5.1) | ||
| HBG2 | ||||
| rs7482144 (XmnI), n (%) | 0.721 | |||
| −/− | 509 (89.6) | 260 (73.4) | ||
| +/− | 57 (10.0) | 90 (25.4) | ||
| +/+ | 2 (0.4) | 4 (1.1) | ||
| KLF1 mutations, n (%) | 0 (0.0) | 12 (3.4) | ||
| Patient characteristics . | Disease severity . | P* . | HWP† . | |
|---|---|---|---|---|
| TM (n = 568) . | TI (n = 354) . | |||
| Gender, n | 373:195 | 217:137 | .179 | |
| Males: Females | ||||
| Age (years), mean ± SD | 6.47 ± 4.24 | 11.81 ± 9.15 | <.001 | |
| Hematological data, mean ± SD | ||||
| Hemoglobin (g/L)‡ | 64.68 ± 17.88 | 71.32 ± 16.93 | <.001 | |
| HbF (g/L)§ | 9.93 ± 9.34 | 25.52 ± 19.09 | <.001 | |
| Requirement for systematic transfusion, n (%) | 568 (100.0) | 132 (37.3) | <.001 | |
| Age at first transfusion (months), median (5th-95th percentile) | 6.0 (2-24) | 24.0 (3-144)|| | <.001 | |
| HBB genotype categories, n (%)¶ | ||||
| β+/β+ | 0 (0.0) | 8 (2.3) | ||
| β+/β0 | 95 (16.7) | 197 (55.6) | ||
| β0/β0 | 473 (83.3) | 149 (42.1) | ||
| HBA genotype categories, n (%)# | ||||
| αα/αα | 508 (89.3) | 271 (76.6) | ||
| –α/αα | 28 (4.9) | 29 (8.2) | ||
| ααT/αα | 5 (0.9) | 9 (2.5) | ||
| —/αα | 27 (4.8) | 40 (11.3) | ||
| –α/αTα | 0 (0.0) | 1 (0.3) | ||
| —/–α | 0 (0.0) | 1 (0.3) | ||
| —/αTα | 0 (0.0) | 3 (0.8) | ||
| BCL11A | ||||
| rs11886868, n (%) | 0.543 | |||
| T/T | 0 (0.0) | 0 (0.0) | ||
| T/C | 29 (5.1) | 8 (2.3) | ||
| C/C | 539 (94.9) | 346 (97.7) | ||
| rs766432, n (%) | 0.646 | |||
| A/A | 345 (60.7) | 166 (49.6) | ||
| A/C | 192 (33.8) | 163 (46.0) | ||
| C/C | 31 (5.5) | 25 (7.1) | ||
| HBS1L-MYB intergenic region | ||||
| rs9399137, n (%) | 0.627 | |||
| T/T | 398 (70.1) | 220 (62.1) | ||
| T/C | 155 (27.3) | 116 (32.8) | ||
| C/C | 15 (2.6) | 18 (5.1) | ||
| HBG2 | ||||
| rs7482144 (XmnI), n (%) | 0.721 | |||
| −/− | 509 (89.6) | 260 (73.4) | ||
| +/− | 57 (10.0) | 90 (25.4) | ||
| +/+ | 2 (0.4) | 4 (1.1) | ||
| KLF1 mutations, n (%) | 0 (0.0) | 12 (3.4) | ||
Definition of TM/TI in this study is based on the following 4 clinical indications23,24 : (1) onset of anemia: <6 months, 6-24 months (TM), or >24 months (TI); (2) transfusion before 4 years of age: symptomatic anemia requiring more than 8 transfusions/year before 4 years of age (TM) or none/occasional transfusion before 4 years of age (TI); (3) steady-state hemoglobin levels: <60 g/L (TM) or 60-100 g/L (TI); (4) liver/spleen enlargement: severe (>4 cm) (TM) or moderate (0-4 cm) (TI); and (5) growth and development: delayed (TM) or normal (TI).
P value was determined using either a Mann-Whitney U test or the χ2 test as appropriate in comparing clinical data between TM and TI.
P for the Hardy-Weinberg equilibrium test of rs11886868, rs766432, rs9399137, and rs7482144 in 922 individuals.
Hemoglobin levels were untransfused or pretransfusion data.
HbF (g/L) was calculated from total Hb level and HbF (%).
Very few patients were classified as TI according to clinical diagnostic criteria, although they underwent their first transfusion before 6 months of age. In these cases, the reason for early transfusion was recorded as managing an acute hemolysis resulting from infections during early infancy.
HBB genotype categories were defined as follows: (β0) CD41/42-TTCT (40.0%), CD17 A>T (28.2%), IVS2-654 C>T (6.2%), CD71/72 +A (4.7%), IVS1-1 G>T (2.5%), CD43 G>T (1.1%), CD27/28 +C (0.2%), CD30 A>G (0.1%), CD14/15 +G (0.1%), CD38-A (0.1%), IVS2-1 G>A (0.1%), IVS1-130 G>C (0.1%); (β+) −28 A>G (9.0%), CD26 G>A (5.6%), −29 A>G (1.1%), IVS2-5 G>C (0.7%), −90 C>T (0.2%), −31 A>G (0.1%), and IVS1-5 G>C (0.1%).
HBA genotype categories were defined as: –α: –α3.7, –α4.2; —:—SEA; αT: αCS, αWS.