江苏地区汉族儿童多药耐药基因3个单核苷酸多态性位点的单倍型研究

目的分析江苏汉族人群多药耐药基因-1（MDR1）的单核甘酸多态（12外显子1236C→T突变、21外显子2677G→T/A突变、26外显子3435C→T突变）及其构成的单倍型分布。方法通过多重单碱基延伸反应（SNaPshotSNP分型技术）对江苏地区170名健康儿童的MDR1C1236T、G2677T/A、C3435T的SNP位点进行基因分型,统计各基因型频率。UNPHASED软件对MDR1的SNPs（C1236T-G2677T/A-C3435T）进行单倍型分析。结果在170例儿童中,等位基因1236T、2677T、2677A、3435T频率分别为63.5%、37.4%、17.0%和35.0%。基因型频率分布符合Hardy-Weinberg平衡（HWE）,差异无统计学意义（P〉0.05）。MDR1的1236、2677、3435三个位点间（C1236T-G2677T/A-C3435T）存在连锁不平衡性,以TTT（31.8%）、TGC（25.3%）、CGC（17.7%）和CAC（16.2%）四种单倍型为主。结论江苏地区汉族人群MDR1的单核甘酸多态及单倍型分布具有自己的特点。在临床应用相关药物时,进行基因型及单倍型检测,将有助于指导临床个体化用药。

Haplotypes study of three single nucleotide polymorphisms in multidrug resistance gene 1 in han nationality of Jiangsu province in China

Objective To investigate the single nucleotide polymorphisms (SNPs) and the distribution of their haplotypes in exon 12 C1236T,exon 21 G2677T/A and exon 26 C3435T of the multidrug resistance 1 (MDR1) gene in Han nationality of Jiangsu,China.Methods SNaPshot SNP typing was used to determine the genotypes of MDR1 C1236T,G2677T/A,C3435T in 170 healthy objects.The software UNPHASED was used for haplotype frequencies analysis.Results Of 170 chilidren,the frequency of 1236T allele,2677T allele,2677A allele and 3435T allele were 63.5%,37.4%,17.0% and 35.0%,respectively.The allelic distribution complied well with Hardy-Weinberg Equilibrium(HWE),and the differences were of no significance(P>0.05).The data show evidence of pairwise linkage disequilibrium between the three common SNPs (C1236T,G2677T/A,C3435T).Haplotypes TTT(31.8%),TGC(25.3%),CGC(17.7%) and CAC(16.2%) were predominant.Conclusion The MDR1 SNPs and haplotypes distribution in Jiangsu Han population has its own characteristics.To determine the genotyping and haplotypes will be helpful for guiding individualized medication during the clinical application of associative drugs.