天然放射性高本底辐射地区汉族人群MGMT基因遗传多态性单体型分析

Analysis on polymorphism haplotypes of MGMT gene in the population of high background radiation areas

目的探讨MGMT基因5'侧翼区及第一编码区多态性单体型在天然放射性高本底地区汉族人群中的分布特征。方法随机选取60例广东高本底地区汉族人群为研究对象,以人MGMT基因目的片段(-875nt^+362nt)中-797G>A、-245T>G、-177T>G、-19C>T、+73C>T和+336G>A共6个多态性位点纳入本研究,采用HaploView软件分析其遗传学特征、连锁不平衡和单体型分布。结果60例高本底地区人群中各遗传多态性位点基因型频率均符合Hardy-Weinberg平衡(P>0.05);各位点在该人群的杂合度不同,分别为-797G>A(0.208)、-245T>G(0.017)、-177T>G(0.049)、-19C>T(0.269)、+73C>T(0.269)和+336G>A(0.417),且-245T>G和-177T>G均不存在变异纯合基因型;连锁不平衡分析结果表明-797G>A与-19C>T、-797G>A与+73C>T均呈较强的连锁不平衡关系,-19C>T与+73C>T之间呈完全连锁不平衡关系。构建了该人群中5种多态性单体型,其中最主要的野生单体型(H1)频率为51.4%,其他4种为变异单体型(H2~H5),频率为46.3%。-19C>T与+73C>T之间形成1个单体型域,构成2种代表性域内单体型(CC/TT)。结论首次确认并报道广东天然放射性高本底地区汉族人群中MGMT基因5'侧翼区和第一编码区6个遗传多态性位点及其单体型(域)分布。

Objective To understand the distribution of polymorphism haplotypes of MGMT gene in the population of high background radiation areas. Methods Sixty healthy residents with Han nationality were ran- domly selected from high background radiation areas in Guangdong. The genetic variants at-875nt ～ ＋362nt locus of MGMT were identified by direct sequencing. HaploView software was used to analyze the genetic characteristics, the linkage disequilibrium and the haplotype distribution. Results The genotype frequencies of all Six genetic polymorphisms were in Hardy weinberg equilibrium （P〉0.05） . The heterozygosities （7） of each polymorphismwere-797G〉A （0.208）, -245T〉G （0.017）, -177T〉G （0.049）, -19C〉T （0. 269）, ＋73C〉T （0. 269） and ＋336G〉A （0. 417）, respectively. The polymorphisms were in strong LD between -97G〉A and -19C〉T, -797G〉A and -73C〉T, respectively. Complete LD was found between -19C〉T and ＋73C〉T. Five major haplotypes were identified with the frequency of wild type hapto- type （H1） of 51.4% and the rest （H2-H5） of 46.3%. One haplotype domain was identified with the representative one of --19C〉T and ＋73C〉T. Conclusions The six genetic polymorphisms and their hap- lotypes are identified and reported for the first time in the 5＇-flanking region and first coding region of MGMT gene among residents with Han nationality in high background areas.