The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design, Subjects and Definitions
2.2. rs6903608 Genotyping
2.3. Statistical Analysis
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Value (n = 161) |
---|---|
Female sex, n (%) | 124 (77) |
Age at first iTTP episode, median (IQR) | 45 (33 to 54) |
Clinical characteristics | |
Concomitant autoimmune disease, n (%) * | 19 (12) |
Infectious trigger, n (%) | 37 (24) |
Platelet count, ×109/L, median (IQR) † | 13 (8 to 20) |
Hemoglobin, g/dL, median (IQR) † | 8.0 (6.9 to 9.6) |
LDH, IU/L, median (IQR) † | 1418 (748 to 2340) |
rs6903608 Genotype | Cases (n = 161) | Controls (n = 456) | OR (95% CI) |
---|---|---|---|
Genotypic model | |||
TT, n (%) | 20 (12) | 119 (26) | Reference |
CT, n (%) | 67 (42) | 243 (53) | 1.64 (0.95 to 2.83) |
CC, n (%) | 74 (46) | 94 (21) | 4.68 (2.67 to 8.23) |
Dominant model | |||
TT, n (%) | 20 (12) | 119 (26) | Reference |
CT + CC, n (%) | 141 (88) | 337 (74) | 2.49 (1.49 to 4.16) |
Recessive model | |||
TT + CT, n (%) | 87 (54) | 362 (79) | Reference |
CC, n (%) | 74 (46) | 94 (21) | 3.28 (2.23 to 4.81) |
Sex | rs6903608 Genotype | Cases (n = 161) | Controls (n = 456) | OR (95%CI) |
---|---|---|---|---|
Male, n (%) | TT | 2 (1) | 27 (6) | Reference |
CT | 14 (9) | 71 (16) | 2.66 (0.57 to 12.50) | |
CC | 21 (13) | 22 (5) | 12.89 (2.72 to 61.07) | |
Female, n (%) | TT | 18 (11) | 92 (20) | 2.64 (0.58 to 12.11) |
CT | 53 (33) | 172 (38) | 4.16 (0.96 to 18.07) | |
CC | 53 (33) | 72 (16) | 9.94 (2.26 to 43.63) |
Concomitant Autoimmune Disorder | Infectious Trigger * | ||||||||
---|---|---|---|---|---|---|---|---|---|
Absent (n = 142) | Present (n = 19) | Absent (n = 119) | Present (n = 37) | Controls (n = 456) | |||||
rs6903608 | n (%) | OR (95%CI) | n (%) | OR (95%CI) | n (%) | OR (95% CI) | n (%) | OR (95%CI) | n (%) |
TT | 14 | Ref. | 6 | Ref. | 16 | Ref. | 4 | Ref. | 119 (26) |
CT | 61 | 2.13 (1.15 to 3.97) | 6 | 0.49 (0.16 to 1.55) | 50 | 1.53 (0.84 to 2.80) | 14 | 1.71 (0.55 to 5.32) | 243 (53) |
CC | 67 | 6.06 (3.21 to 11.45) | 7 | 1.48 (0.48 to 4.54) | 53 | 4.19 (2.25 to 7.80) | 19 | 6.01 (1.98 to 18.28) | 94 (21) |
rs6903608 Genotype | Age at Onset (Mean, Range) | Mean Difference, 95% CI (Years) |
---|---|---|
TT (n = 20) | 50 (20 to 76) | Reference |
CT (n = 67) | 45 (17 to 79) | 4, −3 to 12 |
CC (n = 74) | 42 (11 to 73) | 7, 0 to 14 |
All iTTP Patients (n = 153) | TT (n = 18) | CT (n = 66) | CC (n = 69) | |
---|---|---|---|---|
Median follow-up time, years (95% CI) * | 4.9 (3.7 to 6.1) | 3.6 (0.0 to 7.5) | 5.8 (5.0 to 6.7) | 4.0 (2.9 to 5.1) |
Relapse n (%) | 44 (29) | 3 (17) | 13 (20) | 28 (41) |
Death n (%) | 3 (2) | 2 (12) | 0 | 1 (1) |
Cancer n (%) | 3 (2) | 0 | 2 (3) | 1 (1) |
Censored alive at the end of study, n (%) | 92 (60) | 12 (67) | 48 (73) | 32 (46) |
Censored alive lost to follow-up, n (%) | 11 (7) | 2 (11) | 3 (5) | 6 (9) |
Cumulative Incidence of Relapse, % (95% CI) | ||||
---|---|---|---|---|
rs6903608 Genotype | at 2 Years | at 4 Years | at 6 Years | at End of Study |
TT (n = 18) | 13 (8 to 22) | 13 (8 to 22) | 30 (23 to 39) | 30 (23 to 39) |
CT (n = 66) | 12 (8 to 17) | 22 (16 to 29) | 22 (16 to 29) | 33 (23 to 46) |
CC (n = 69) | 23 (16 to 32) | 46 (36 to 57) | 46 (36 to 57) | 76 (44 to 97) |
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Mancini, I.; Giacomini, E.; Pontiggia, S.; Artoni, A.; Ferrari, B.; Pappalardo, E.; Gualtierotti, R.; Trisolini, S.M.; Capria, S.; Facchini, L.; et al. The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians. J. Clin. Med. 2020, 9, 3379. https://doi.org/10.3390/jcm9103379
Mancini I, Giacomini E, Pontiggia S, Artoni A, Ferrari B, Pappalardo E, Gualtierotti R, Trisolini SM, Capria S, Facchini L, et al. The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians. Journal of Clinical Medicine. 2020; 9(10):3379. https://doi.org/10.3390/jcm9103379
Chicago/Turabian StyleMancini, Ilaria, Elisa Giacomini, Silvia Pontiggia, Andrea Artoni, Barbara Ferrari, Emanuela Pappalardo, Roberta Gualtierotti, Silvia Maria Trisolini, Saveria Capria, Luca Facchini, and et al. 2020. "The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians" Journal of Clinical Medicine 9, no. 10: 3379. https://doi.org/10.3390/jcm9103379