PRDM9多态性与慢性粒细胞白血病的关联性研究

The association study between PRDM9 polymorphisms and chronic myelogenous leukemia

目的探究PRDM9多态性与慢性粒细胞白血病(CML)遗传易感性的关系。方法应用PCR直接测序技术与DNA单克隆测序技术,对116名Ph染色体及BCR-ABL融合基因阳性CML患者(CML组)和111名健康对照人群(对照组)的PRDM9多态性做DNA序列测定分析;对比CML患者与健康人群的PRDM9多态性分布差异,并通过卡方检验来探究二者之间的关联性。结果在对照组中共发现了7种PRDM9等位基因,其中已命名的有PRDM9-A、B、C、L3及L7,另外2个为新等位基因,分别命名为X1和X2。CML组中共发了10种PRDM9等位基因,除5个已命名等位基因与对照组一样,还发现了5个新等位基因X1、X2、X5、X12及X13。CML组与对照组中PRDM9-A及B等位基因分布为分别为68.10%vs 83.78%,19.40%vs 9.91%(P<0.01),AA基因型分布为41.38%vs 71.17%,AB基因型分布为33.62%vs 15.32%(P<0.01)。此外,PRDM9基因多态性分布在中国汉族与欧洲及非洲人群中存在明显差异(P<0.01)。结论 PRDM9多态性与CML具有关联性,A及AA是CML发生的保护等位基因及基因型,B及AB是CML发生的易感等位基因及基因型。PRDM9基因多态性分布具有人群特异性。

Objective To study the association between PRDM9 polymorphisms and chronic myelogenous leukemia.Methods By using the PCR-based direct sequencing technique and DNA monoclonal sequencing method,PRDM9 polymorphisms in 166 Ph chromosome positive and BCR-ABL positive CML patients and 111 healthy controls were sequenced. Comparative analysis of PRDM9 polymorphism distribution differences between patient and control groups was conducted using the chi--square test to explore the correlation. Results Seven PRDM9 alleles were identified from 111 controls,of which 5 alleles had already been named,PRDM9-A,B,C,L3 and L7. The other 2 alleles were confirmed as new alleles,named X1 and X2,respectively. Ten PRDM9 allele were detected in 116 CML cases,among which the 5 existent alleles were the same as in the control group. Five new alleles,besides the X1,X2,the rest were named as X5,X12 and X13,respectively. The A and B alleles distribution in CML group and the control group were 68. 10% vs 68. 10%,19. 40% vs 9. 91%（ P〈0. 01）.The AA genotype distribution were 41. 38% vs 71. 17%（ P〈0. 01）. In addition,PRDM9 genetic polymorphism distribution was significantly different among Han Chinese,European and African（ P〈0. 05）. Conclusion For the first time,this study discovered the association of PRDM9 polymorphisms with CML. A and AA are protective factors to resist the occurrence of CML,while B and AB are susceptible factors to the occurrence of CML. This study also confirmed that the distribution of PRDM9 possesses population specificities.