人类白细胞抗原基因与重症血液病的相关性

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目的研究 HLA-A、B、DRB1基因与5种常见重症血液病的相关性。方法采用序列特异性引物 PCR(polymerase chain reaction with sequence-specific primers,PCR-SSP)技术,对368例血液病患者进行 HLA 分型,其中急性淋巴细胞白血病(ALL)53例、急性髓细胞白血病(AML)105例、慢性髓细胞白血病(CML)109例、骨髓增生异常综合征(MDS)42例、再生障碍性贫血(AA)59例,并与1000份健康新生儿脐带血进行比较,并计算相对危险度。结果在 ALL 患者中 DRB1~*14的等位基因频率为10.38%,高于对照组的4.70%,差异有统计学意义[X~2=6.849,P=0.009,相对危险度(RR)=2.348];而B~*46和DRB1~*09的等位基因频率分别为1.89%和6.60%,显著低于对照组的6.75%和13.15%,差异有统计学意义(B~*46的 X~2=3.914、P=0.048、RR=0.266,DRB1~*09的 X~2=3.86、P=0.049、RR=0.467)。在 AML 患者中 B~*51的等位基因频率为10.48%,高于对照组的6.80%,差异有统计学意义(X~2=3.869,P=0.049,RR=1.604);在 CML 患者中A~*29和 DRB1~*14的等位基因频率分别为2.75%和8.72%,高于对照组的0.95%和4.70%,差异有统计学意义(A~*29的X~2=4.226、P=0.040、RR=2.951,DRB1~*14的 X~2=6.556、P=0.010、RR=1.936)。在 MDS 患者中 A~*01、B~*54和 B~*57的等位基因频率分别为12.07%、12.07%和6.90%,高于对照组的4.10%、2.80%和1.20%,差异有统计学意义(A~*01的 X~2=6.832、P=0.009、RR=3.21,B~*54的 X~2=13.345、P=0.000、RR=4.765,B~*57的P=0.007、RR:6.099)。在 AA 患者中B~*13、B~*54和 DRB1~*09的等位基因频率分别为17.86%、8.04%和20.34%,高于对照组的11.50%、2.80%和13.15%,差异有统计学意义(B~*13的 X~2=4.107、P=0.043、RR=1.673,B~*54的 X~2=8.071、P=0.004、RR=3.033,DRB1~*09的 X~2=4.916、P=0.027、RR=1.686);而DRB1~*03的等位基因频率为0.85%,低于对照组的5.10%,差异有统计学意义(X~2=4.355,P=0.037,RR=0.159)。结论不同血液病分别与不同 HLA基因有显著的相关性,这对血液病的病因研究有重要意义。 Objective To study the association between HLA-A, B and DRB1 genes and five common severe hematological diseases. Methods HLA-typing was performed on 368 patients with hematological diseases using polymerase chain reaction with sequence-specific primers (PCR-SSPs), including 53 cases of acute lymphoblastic leukemia (ALL), 6 cases of acute myeloid leukemia AML 105 cases, 109 cases of chronic myeloid leukemia (CML), 42 cases of myelodysplastic syndrome (MDS), 59 cases of aplastic anemia (AA), and compared with the cord blood of 1000 healthy newborns, and calculated Relative risk. Results The allele frequency of DRB1 ~ * 14 in ALL patients was 10.38%, which was significantly higher than that in the control group (4.70%) [X ~ 2 = 6.849, P = 0.009 and relative risk (RR) = 2.348 The allele frequencies of B ~ * 46 and DRB1 ~ * 09 were 1.89% and 6.60%, respectively, which were significantly lower than those of the control group (6.75% and 13.15%, respectively) 2 = 3.914, P = 0.048, RR = 0.266, X ~ 2 = 3.86 for DRB1 ~ * 09, P = 0.049, RR = 0.467). The allele frequency of B ~ * 51 in AML patients was 10.48%, which was significantly higher than that in the control group (6.80%) (X ~ 2 = 3.869, P = 0.049, RR = 1.604) The allele frequencies of A ~ * 29 and DRB1 ~ * 14 were 2.75% and 8.72% respectively, which were significantly higher than those of the control group (0.95% and 4.70%, respectively) P = 0.040, RR = 2.951, X ~ 2 of DRB1 ~ * 14 = 6.556, P = 0.010, RR = 1.936). The allele frequencies of A ~ * 01, B ~ * 54 and B ~ * 57 were 12.07%, 12.07% and 6.90% in MDS patients, respectively, which were 4.10%, 2.80% and 1.20% higher than those in control subjects Statistical significance (X ~ 2 = 6.832, P = 0.009, RR = 3.21 for A ~ * 01, X ~ 2 = 13.345 for B ~ * 54, P = 0.000, RR = 4.765, P = 0.007 for B ~ * 57 , RR: 6.099). The allele frequencies of B ~ * 13, B ~ * 54 and DRB1 ~ * 09 in patients with AA were 17.86%, 8.04% and 20.34% respectively, which were significantly higher than those in control group (11.50%, 2.80% and 13.15% Statistical significance (X ~ 2 = 4.107, P = 0.043, RR = 1.673 for B ~ * 13, X ~ 2 = 8.071 for B * 54, P = 0.004, RR = 3.033, X ~ 2 for DRB1 ~ * 09 = 4.916, P = 0.027, RR = 1.686). The allele frequency of DRB1 ~ * 03 was 0.85%, which was lower than that of control group (5.10% RR = 0.159). Conclusion Different hematological diseases have significant correlation with different HLA genes, which is of great significance for the study of the etiology of hematological diseases.
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