南方汉族KIR-HLA系统分子遗传多态性与急性白血病的相关性

Association of molecular genetic polymorphism of KIR-HLA systems with acute leukemia in Southern Chinese Han

目的探讨中国南方汉族人群KIR-HLA系统分子遗传多态性与急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)、急性髓系白血病(acute myelocytic leukemia,AML)的相关性。方法对323份成年ALL、350份成年AML患者以及745份随机健康对照的样本,采用PCR-序列特异性引物(sequence specific primer,SSP)方法检测KIR基因,采用测序分型法进行HLA-A、-B、-C基因分型。从KIR基因、KIR基因组合型、HLAⅠ类配体、已知的KIR+HLA受-配体组合等4个方面比较各病例组与对照组分子遗传多态性的差异。结果ALL及AML病例组中分别检出了32种、33种KIR基因组合型,与对照组中检出的35种KIR基因组合型相比,AA1在ALL组和AML组的检出频率均显著低于健康对照组(ALL组:45.79%vs.55.30%,P_(c)=0.004;AML组:48.27%vs.55.30%,P_(c)=0.030),为急性白血病保护性因素;ALL组中2DL2及其受-配体组合2DL2+HLA-C1、2DS2及其受-配体组合2DS2+HLA-C1的检出频率均显著高于健康对照组,而2DL3基因、HLA-A3/A11配体及3DL2+HLA-A3/A11受-配体组合的检出频率均显著低于健康对照组(P<0.05),但经过Bonferroni校正后差异显著性均丢失(P_(c)>0.05);AML组2DS1和2DL5的检出频率均显著高于健康对照组,而HLA-C2配体及2DL1+HLA-C2受-配体组合的检出频率均显著低于健康对照组(P<0.05),但经过Bonferroni校正后差异显著性均丢失(P_(c)>0.05)。结论本文获得了南方汉族KIR-HLA系统中与急性白血病相关的潜在易感或保护性因素,尤其是保护性因素AA1基因组合型,可为急性白血病发病机制和个体化免疫治疗提供新的线索及理论依据。

Objective To investigate the association of molecular genetic polymorphism of KIR-HLA systems with acute lymphoblastic leukemia(ALL)and acute myelocytic leukemia(AML)in southern Chinese Han.Methods A total number of 323 cases of adult ALL patients,350 adult AML,and 745 random healthy controls were tested by KIR PCR-SSP and HLA-A,-B,-C sequence-based typing(PCR-SBT)methods.The molecular genetic polymorphisms of KIR genes and KIR gene profiles,classⅠHLA ligands,and KIR receptor+HLA ligand combinations were compared between patient and healthy control groups.Results A total number of 32 and 33 different kinds of KIR profiles were identified in the ALL and AML patient groups.Compared with the observed frequencies of KIR profiles in healthy controls,the observed frequencies of KIR profile AA1 were significantly lower in both the ALL and AML groups(ALL group:45.79%vs.55.30%,P_(c)=0.004;AML group:48.27%vs.55.30%,P_(c)=0.030).In the ALL group,the observed frequencies of 2DL2 gene and 2DL2+HLA-C1 combination,2DS2 gene and 2DS2+HLA-C1 combination were significantly higher than those in healthy controls(P<0.05),whereas the frequencies of 2DL3 gene,HLA-A3/A11 ligand and 3DL2+HLA-A3/A11 combination were significantly lower than those in healthy controls.However,no significant differences remained after Bonferroni correction(P_(c)>0.05).In AML group,the observed frequencies of both 2DS1 and 2DL5 genes were significantly higher than that in healthy controls,whereas the frequencies of HLA-C2 ligand and 2DL1+HLA-C2 combination were significantly lower than that in healthy controls(P<0.05).However,no significant difference existed after Bonferroni correction(P_(c)>0.05).Conclusion This study revealed some potential susceptibility or protective factors related to acute leukemia in southern Chinese Han,especially the protective factor KIR profile AA1,which might provide new clues and theoretical basis for the pathogenesis of acute leukemia and individualized immunotherapy.