Chen Nanying, Wang Fang, Zhao Yanmin, Dong Lina, Wang Wei, Zhang Wei, He Ji, Zhu Faming
HLA Typing Laboratory, Blood Center of Zhejiang Province, Hangzhou, China.
HLA Typing Laboratory, Key Laboratory of Blood Safety Research of Zhejiang Province, Hangzhou, China.
Int J Immunogenet. 2023 Oct;50(5):233-242. doi: 10.1111/iji.12629. Epub 2023 Jul 23.
The association between HLA loci and haematological malignancy has been reported in certain populations. However, there are limited data for HLA loci at a high-resolution level with haematological malignancy in China. In this study, a total of 1115 patients with haematological malignancies (including 490 AML, 410 acute lymphoblastic leukaemia (ALL), 122 myelodysplastic syndrome [MDS] and 93 non-Hodgkin's lymphoma [NHL]) and 1836 healthy individuals as a control group in the Han population of Zhejiang Province, China, were genotyped for HLA-A, HLA-C, HLA-B, HLA-DRB1 and HLA-DQB1 loci at high resolution. The possible association between HLA alleles and haplotypes and haematologic malignancy was analysed. The allele frequencies (AFs) of HLA-A02:05, HLA-A02:06, HLA-A32:01, HLA-B35:03, HLA-B54:01, HLA-B55:07, HLA-DRB104:05, HLA-DRB115:01, HLA-DQB104:01 and HLA-DQB106:02 in the MDS patients were much higher than those in the control group (P < 0.05), while the AFs of HLA-C07:02, HLA-DRB103:01, HLA-DRB114:54, HLA-DQB102:01 and HLA-DQB105:03 were obviously lower than those in the control group (p < .05). Interestingly, the differences in these HLA alleles in patients with MDS were not significant after applying Bonferroni correction (Pc > .05), except for HLA-A02:06 (Pc < .01). There were 13, 6 and 10 HLA alleles with uncorrected significant differences (p < .05) among patients with AML, ALL and NHL, respectively, compared with those in the control group, but the differences in these HLA alleles were not significant after correction (Pc > .05). Compared to those of the control group, there were some haplotypes over 1.00% frequency in patients with AML, MDS and NHL patients with uncorrected significant differences (p < .05). However, none of them showed a significant difference after correction as well (Pc > .05). The study reveals that HLA-A*02:06 may lead to susceptibility to MDS, but none of the HLA alleles were associated with AML, ALL or NHL after correction. These data will help to further understand the role of HLA loci in the pathogenesis of haematological malignancy in China.
在某些人群中，已报道了HLA基因座与血液系统恶性肿瘤之间的关联。然而，在中国，关于高分辨率水平下HLA基因座与血液系统恶性肿瘤的数据有限。在本研究中，对中国浙江省汉族人群中1115例血液系统恶性肿瘤患者（包括490例急性髓系白血病、410例急性淋巴细胞白血病、122例骨髓增生异常综合征和93例非霍奇金淋巴瘤）以及1836名健康个体作为对照组，进行了HLA - A、HLA - C、HLA - B、HLA - DRB1和HLA - DQB1基因座的高分辨率基因分型。分析了HLA等位基因和单倍型与血液系统恶性肿瘤之间可能的关联。骨髓增生异常综合征患者中HLA - A02:05、HLA - A02:06、HLA - A32:01、HLA - B35:03、HLA - B54:01、HLA - B55:07、HLA - DRB104:05、HLA - DRB115:01、HLA - DQB104:01和HLA - DQB106:02的等位基因频率远高于对照组（P < 0.05），而HLA - C07:02、HLA - DRB103:01、HLA - DRB114:54、HLA - DQB102:01和HLA - DQB105:03的等位基因频率明显低于对照组（p < 0.05）。有趣的是，除HLA - A02:06（Pc < 0.01）外，骨髓增生异常综合征患者中这些HLA等位基因在应用Bonferroni校正后差异无统计学意义（Pc > 0.05）。与对照组相比，急性髓系白血病、急性淋巴细胞白血病和非霍奇金淋巴瘤患者中分别有13个、6个和10个未校正时有显著差异（p < 0.05）的HLA等位基因，但校正后这些HLA等位基因的差异无统计学意义（Pc > 0.05）。与对照组相比，急性髓系白血病、骨髓增生异常综合征和非霍奇金淋巴瘤患者中一些单倍型频率超过1.00%，未校正时有显著差异（p < 0.05）。然而，校正后它们也均无显著差异（Pc > 0.05）。该研究表明，HLA - A*02:06可能导致骨髓增生异常综合征易感性，但校正后没有HLA等位基因与急性髓系白血病、急性淋巴细胞白血病或非霍奇金淋巴瘤相关。这些数据将有助于进一步了解HLA基因座在中国血液系统恶性肿瘤发病机制中的作用
