葡萄糖激酶基因4个标签单核苷酸多态性位点与2型糖尿病的相关性研究

摘要

Objective To investigate the relationships between Glucokinase(GCK) gene 4 tag single‐nucleotide polymorphisms , tagSNPs)sites which named rs12702070 ,rs2268569 ,rs2268573 and rs1476891 polymorphisms and type 2 diabetes in Chinese South‐ern Han Population .Methods This study was designed as a case‐control .499 type 2 diabetes patients and 499 healthy controls were chosen .4 GCK tagSNPs sites were analyzed by improved multiple ligase detection reaction(iMLDR) ,and genotype and allele fre‐quency between T2D group and healthy controls could be determined by chi‐square test ,logistic regression analysis ,and tagSNPs were further analyzed under three genetic modes(dominant ,recessive and additive) .What′s more ,Haploview software was used to construct the haplotype of 4 GCK tagSNPs and the linkage disequilibrium(LD) and relationship between various GCK haplotype and T2D susceptibility could be analyzed .Results Genotype distribution of rs2268573 ,rs2268569 and rs1476891 and allele frequen‐cy in T2D group were no significant differences with health controls .Significant differences in genotype distribution of rs12702070 and allele frequency were observed between T2D group and health controls .Under dominant model and additive model ,genotype distribution of rs12702070 in T2D was significantly different from health controls .One LD domain was observed in 3 tagSNPs a‐mong those 4 sites of GCK gene .There are 4 main haplotypes(TAG ,TGG ,TAT ,CGG)in rs2268569 ,rs12702070 and rs1476891 , but all these haplotypes have no relevance to the individual risk of T2D(P>0 .05) .Conclusion The results indicated that the GCK gene tagSNPs site rs12702070 imparts susceptibility to T2D in Han Chinese ,but not rs2268573 ,rs2268569 and rs1476891 .Four main haplotypes in rs2268569 ,rs12702070 and rs1476891 have no relevance to T2D .%目的：探讨葡萄糖激酶（GCK）基因4个标签单核苷酸多态性（tagSNPs）位点 rs12702070、rs2268569、rs2268573、rs1476891与2型糖尿病（T2D）的关系。方法选取中山大学附属中山医院住院的中国南方汉族 T2D患者499例（T2D组），同时选择汉族健康人499例作为对照组，对GCK基因的4个tagSNPs位点进行基因分型并检测样本代表性。比较 T2D组和对照组基因型和等位基因频率的差异，并在3种遗传模型下对各SNP位点进行相关性分析。构建GCK基因4个 tagSNPs位点的单体型，分析是否存在连锁不平衡（LD）及不同的GCK单体型与T2D易感性的关系。结果 rs2268573、rs2268569、rs1476891的基因型和等位基因频率在T2D组和对照组之间差异均无统计学意义。rs12702070的基因型和等位基因分布在D2M组和对照组之间差异有统计学意义，且在显性遗传模式下以及在加性遗传模式下其基因型分布在两组之间差异有统计学意义。GCK基因4个位点中rs2268569、rs12702070和rs1476891有1个LD域，其中共存四种主要单体型，均与个体患T2D的风险无相关性。结论在汉族人群中，GCK基因区域的rs12702070位点与糖尿病遗传易感性密切相关，而rs2268573、rs2268569、rs1476891位点与糖尿病遗传易感性无明确相关性。rs2268569、rs12702070、rs1476891 LD域四种主要单体型均与个体患T2D的风险无相关性。