Relationship between glucokinase gene 6 tag single nucleotide polymorphism sites and type 2 diabetes mellitus
10.3760/cma.j.issn.1009-9158.2015.12.009
- VernacularTitle:葡萄糖激酶基因6个标签单核苷酸多态性位点与2型糖尿病的相关性研究
- Author:
Xiuming ZHANG
;
Geqin SUN
;
Jingjing LI
;
Hui HAN
;
Qiong CHEN
- Publication Type:Journal Article
- Keywords:
Diabetes mellitus,type 2;
Glucokinase;
Polymorphism,single nucleotide
- From:
Chinese Journal of Laboratory Medicine
2015;38(12):827-832
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the relationships between Glucokinase (GCK) gene 6 (tag single-nucleotide polymorphisms,tagSNPs)sites which named rs12702070,rs2971672,rs2268569,rs2268573,rs2300587 and rs1476891 polymorphisms and type 2 diabetes in Chinese Southern Han Population.Methods This study was designed as a case-control.499 type 2 diabetes patients and 499 healthy controls were chosen.All subjects were from August 2013 to December 2014 in Zhongshan Affiliated Hospital of Sun Yat-sen University.6 GCK tagSNPs sites were analyzed by improved multiple ligase detection reaction (iMLDR),and genotype and allele frequency 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 6 GCK tagSNPs and the linkage disequilibrium (LD) and relationship between various GCK haplotype and T2D susceptibility could be analyzed.Results Genotype distribution of rs2268573,rs2300587,rs2268569 and rs1476891 (x2 were 3.361,2.076,0.582 and 0.918 respectively,all P ＞0.05) and allele frequency (x2 were 0.222,1.980,0.590 and 0.851 respectively,all P ＞ 0.05) in T2D group were no significant differences with health controls.Significant differences in genotype distribution of rs2971672 and rs12702070 (x2 were 6.896 and 7.990 respectively,all P ＜ 0.01) and allele frequency (x2 were 4.708 and 5.979,P ＜ 0.05 and P ＜ 0.01 respectively) were observed between T2D group and health controls.Under dominant model (rs2971672:OR =1.74,95％ CI =1.17-2.57,P ＜ 0.01;rs12702070:OR =1.54,95 ％ CI =1.17-2.04,P ＜ 0.01) and additive model (rs2971672:OR =1.51,95 ％ CI =1.06-2.14,P ＜ 0.05;rs12702070:OR =1.26,95％ CI =1.04-1.52,P ＜ 0.05),Genotype distribution of rs2971672 and rs2971672 in T2D were significantly different from health controls.There are two LD domains in 5 tagSNPs among those 6 sites of GCK gene.There are three main haplotypes(TC,TA,CA)in rs2971672 and rs2300587,and four main haplotypes (TAG,TGG,TAT,CGG) in Rs2268569,rs12702070 and rs1476891.Although TAG,TGG,TAT and CGG have no relevance to the individual risk of T2D (P ＞ 0.05),haplotype TA and CA reduce the individual risk of T2D with OR 0.81 (95％ CI:0.66-1.00,P＜0.05) and0.78 (95％ CI:0.62-0.98,P ＜0.01)respectively.Conclusions The results indicated that GCK gene 2 tagSNPs sites included rs2971672 and rs12702070 imparts susceptibility to T2D in Han Chinese,but not rs2268573,rs2300587,rs2268569 and rs1476891.Haplotype TA and CA in rs2971672 and rs2300587 reduce the individual risk of T2D and four main haplotypes (TAG,TGG,TAT,CGG) in rs2268569,rs12702070 and rs1476891 have no relevance to T2D.
