Kornblit Brian, Enevold Christian, Wang Tao, Spellman Stephen, Haagenson Mike, Lee Stephanie J, Müller Klaus
The Laboratory for Allogeneic Hematopoietic Cell Transplantation, Department of Hematology, Rigshospitalet, Copehnhagen, Denmark.
Department of Infectious Diseases and Rheumatology, Institute for Inflammation Research, Rigshospitalet, Copenhagen, Denmark.
Biol Blood Marrow Transplant. 2015 Feb;21(2):259-65. doi: 10.1016/j.bbmt.2014.09.016. Epub 2014 Nov 20.
To assess the impact of the genetic variation in toll-like receptors (TLRs) on outcome after allogeneic myeloablative conditioning hematopoietic cell transplantation (HCT), we investigated 29 single nucleotide polymorphisms across 10 TLRs in 816 patients and donors. Only donor genotype of TLR8 rs3764879, which is located on the X chromosome, was significantly associated with outcome at the Bonferroni-corrected level P ≤ .001. Male hemizygosity and female homozygosity for the minor allele were significantly associated with disease-free survival (hazard ratio [HR], 1.47 [95% confidence interval {CI}, 1.16 to 1.85]; P = .001). Further analysis stratified by donor sex due to confounding by sex was suggestive for associations with overall survival (male donor: HR, 1.41 [95% CI, 1.09 to 1.83], P = .010; female donor: HR, 2.78 [95% CI, 1.43 to 5.41], P = .003), disease-free survival (male donor: HR, 1.45 [95% CI, 1.12 to 1.87], P = .005; female donor: HR, 2.34 [95% CI, 1.18 to 4.65], P = .015), and treatment-related mortality (male donor: HR, 1.49 [95% CI, 1.09 to 2.04], P = .012; female donor: HR, 3.12 [95% CI, 1.44 to 6.74], P = .004). In conclusion, our findings suggest that the minor allele of TLR8 rs3764879 of the donor is associated with outcome after myeloablative conditioned allogeneic HCT.
为评估Toll样受体（TLR）基因变异对异基因清髓性预处理造血细胞移植（HCT）后预后的影响，我们对816例患者和供者的10种TLR中的29个单核苷酸多态性进行了研究。位于X染色体上的TLR8 rs3764879，仅供者基因型在Bonferroni校正水平P≤0.001时与预后显著相关。次要等位基因的男性半合子和女性纯合子与无病生存率显著相关（风险比[HR]，1.47[95%置信区间{CI}，1.16至1.85]；P = 0.001）。由于性别混杂因素，按供者性别分层的进一步分析提示与总生存率相关（男性供者：HR，1.41[95%CI，1.09至1.83]，P = 0.010；女性供者：HR，2.78[95%CI，1.43至5.41]，P = 0.003）、无病生存率（男性供者：HR，1.45[95%CI，1.12至1.87]，P = 0.005；女性供者：HR，2.34[95%CI，1.18至4.65]，P = 0.015）以及治疗相关死亡率（男性供者：HR，1.49[95%CI，1.09至2.04]，P = 0.012；女性供者：HR，3.12[95%CI，1.44至6.74]，P = 0.004）。总之，我们的研究结果表明，供者TLR8 rs3764879的次要等位基因与清髓性预处理异基因HCT后的预后相关。
