结直肠癌患者DNA甲基转移酶3A、3B基因单核苷酸多态性观察

Observation of DNA methyltransferase-3A and 3B gene single nucleotide polymorphism of patients with colorectal cancer

目的观察结直肠癌(CRC)患者DNA甲基转移酶(DNMT)3A、3B基因单核苷酸多态性特点,为CRC发病机制的研究提供依据。方法对89例CRC患者(观察组)和94例体检健康者(对照组)的血液标本进行DNA提取,应用Sequenom MassArray质谱阵列分析技术对DNMT3A rs1550117、rs13420827、rs11887120、rs13428812和DNMT3B rs6119954、rs4911259、rs4911107、rs1569686、rs2424908、rs2424932共10个单核苷酸多态性位点(SNPs)分析,判断各位点与CRC的关联。结果 DNMT3A的4个位点之间不存在紧密连锁,DNMT3B的6个位点相互间均呈强连锁不平衡(r2>0.8),形成的4种单体型中以TGTAGG和CATAGG为主,rs6119954和rs2424908的等位基因频率在观察组和对照组间差异有统计学意义(P<0.05)。结论 CRC患者DNMT3B rs6119954和rs2424908的等位基因频率明显增高,此为CRC发病机制的研究提供了依据。

Objective To observe and analyze the characteristics of DNA methyhransferase（ DNMT）-3A and 3B gene single nucleotide polymorphisms of colorectal cancer（CRC）, and then to provide the evidence for CRC pathogenesis research. Methods Genomic DNA was extracted from the leukocyte cell of blood samples collected from 89 CRC patients （observation group）. The same samples were collected from the other 94 control subjects （control group）. Sequenom Mas- sArray system was used to analyze ten SNPs of DNMT3A （rs1550117, rs13420827, rs11887120, rs13428812） and DN- MT3 B （ rs6119954, rs4911259, rs4911107, rs1569686, rs2424908, rs2424932）. The association between the SNPs and CRC was analyzed. Results The data showed no evidence of pairwise linkage disequilibrium between the four SNPs of DNMT3A. Strong linkage disequilibrium was found among the six SNPs of DNMT3B （r2 〉 0.8 ）. TGTAGG and CATAGG were predominant in the four haplotypes. There were significant differences between the cases and the controls in the allele frequency of SNPs rs6119954 and rs2424908 （ P 〈 0. 05 ）. Conclusion The allele frequencies of rs6119954 and rs2424908 are significant higher in CRC patients than healthy people, which provide the evidence for colorectal cancer pathogenesis research.