湖北汉族人群多药耐药基因多态性与大肠癌的相关性

Relationship between genetic polymorphism of multidrug resistance 1 gene and the risk of sporadic colorectal carcinoma in Hubei Han population of China

目的 探讨湖北汉族人群多药耐药基因（MDR1）3个位点的单核苷酸多态（1b外显子-129T→C突变、21外显子2 677G→T/A突变、26外显子3 435C→T突变）与大肠癌的相关性.方法 通过多重单碱基延伸反应[SNaPshot单核苷酸多态性（SNP）分型技术]检测133例大肠癌患者和383例对照组的MDR1 T-129C、G2 677T/A、C3 435T基因型分布.统计各位点基因型频率以及T-129C-G2 677T/A-C3 435T单倍体型频率.结合临床分型,比较不同基因型、单倍体型与大肠癌发病风险的相关性.结果 MDR1 T-129C位点的基因型分布频率在病例组与对照组差异有统计学意义.病例组中,MDR1 T-129C位点的C等位基因频率（6.4％）明显高于对照组中C等位基因频率（3.4％）,差异有统计学意义（P＜0.05）.MDR1-129位点的基因型TC频率在大肠癌组（12.8％）较对照组（6.3％）显著增高,与大肠癌发病相关[比值比（OR）=2.186,P＜0.05].MDR1的3个位点间-129、2677、3 435存在连锁不平衡性,共检出11种单倍体型（T-129C-G2 677T/A-C3 435T）,其中以TGC （40.27％）、TTT（36.96％）、TAC （9.97％）、TTC （5.02％）4种单倍体型为主.单倍体型CGC、CTT在病例组（1.98％,1.25％）与对照组（0.51％,0.17％）中分布差异有统计学意义（P＜0.05）.单倍体型TGC/TTT在结肠癌组（35.5％）分布频率较直肠癌（15.5％）高（P＜0.05）.结论 MDR1 T-129C的基因多态性与大肠癌易感性明显相关.

Objective To investigate the relationship between genetic polymorphism in prmotor 1b T-129C,exon 21 G2 677T/A and exon 26 C3 435T of the multidrug resistance 1 （MDR1） gene and the risk of sporadic colorectal carcinoma in Hubei Han population of China.Methods A total of 133 patients with colorectal carcinoma and 386 healthy subjects as controls were included.Snapshot single nucleotide polymorphism （SNP） typing was used to determine the allele and genotype frequencies of MDR1 T-129C,C3 435T,and G2 677T/A.Results There was significant difference in the distribution of genotype of MDR1 T-129C between the control group and case group.The mutant heterozygous TC genotype was increased significantly in the case guoup （12.8%） as compared with that in the control group （6.3%）,and was associated with occurrence of colorectal carcinoma [odds ratio （OR） =2.186,P〈0.05].The frequency of-129C allele was increased significantly in the case group as compared with that in the control group （P 〈 0.05）.The data showed the evidence of pairwise linkage disequilibrium among the three common SNPs （T-129C-G2 677T/A-C3 435T）.The haplotypes of TGC （40.27%）,TTT （36.96%）,TAC （9.97%） and TTC （5.02%） were predominant.The haplotype CGC and CTT distributed significantly differently between the case group （1.98% and 1.25%） and control group （0.51% and 0.17%,P 〈 0.05）.The frequency of the haplotype TGC/TTT in the colon carcinoma group （35.5%） was higher than in the rectal carcinoma group （15.5%,P 〈 0.05）.Conclusion The present findings suggest that T-129C polymorphism in MDR1 gene may be a genetic susceptibility factor for sporadic colorectal carcinoma in Hubei Han population of China.