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  

The relationship between glucokinase gene 4 tag single nucleotide polymorphism sites and type 2 diabetes mellitus

作　　者：孙各琴[1] 张秀明[1] 罗楚君 李晶晶[1] 韩慧[1] 陈琼[1] 

机构地区：[1]中山大学附属中山医院医学检验中心,广东中山528403

出　　处：《国际检验医学杂志》2016年第18期2507-2510,共4页International Journal of Laboratory Medicine

基　　金：广东省科技计划基金资助项目(2013B02180012)

摘　　要：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、rs1476891LD域四种主要单体型均与个体患T2D的风险无相关性。Objective To investigate the relationships between Glucokinase（GCK）gene 4tag single-nucleotide polymorphisms,tagSNPs）sites which named rs12702070,rs2268569,rs2268573 and rs1476891polymorphisms and type 2diabetes in Chinese Southern Han Population.Methods This study was designed as a case-control.499 type 2diabetes patients and 499 healthy controls were chosen.4GCK tagSNPs sites were analyzed by improved multiple ligase detection reaction（iMLDR）,and genotype and allele frequency between T2 Dgroup 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 4GCK tagSNPs and the linkage disequilibrium（LD）and relationship between various GCK haplotype and T2 Dsusceptibility could be analyzed.Results Genotype distribution of rs2268573,rs2268569 and rs1476891and allele frequency in T2 Dgroup were no significant differences with health controls.Significant differences in genotype distribution of rs12702070 and allele frequency were observed between T2 Dgroup and health controls.Under dominant model and additive model,genotype distribution of rs12702070 in T2Dwas significantly different from health controls.One LD domain was observed in 3tagSNPs among those 4sites of GCK gene.There are 4main 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 T2 Din Han Chinese,but not rs2268573,rs2268569 and rs1476891.Four main haplotypes in rs2268569,rs12702070 and rs1476891have no relevance to T2 D.

关 键 词：2型糖尿病 基因 葡萄糖激酶 多态性 单核苷酸 

分 类 号：R587.1[医药卫生—内分泌] R440[医药卫生—内科学]