Association Between Single Nucleotide Polymorphisms(SNPs)of ADP-ribosylation Factor-like 15(ARL 15)Gene And The Morbidity Of Type 2 Diabetes Mellitus(T2DM)in Yanbian Chinese Koreans

Objective:To investigate the association between single nucleotide polymorphisms(SNPs)of the gene of ADP-ribosylation-like factor 15(ARL 15)and morbility of type 2 diabetes mellitus(T2DM)in Yanbian Korean populations.Methods:The project was designed as a case-control study.A total of 327 subjects with T2DM(T2DM,n=327),220 subjects with T2DM with hypertension(T2DM+EH,n=220)and 324 age-and gender-matched control subjects with normal glucose tolerance(NGT,n=324)were involved in this study.The genotypes and alleles of SNPs rs26770,rs4311394 and rs35941 were determined by the method of SnaPshot oRoRoRoR(?)Multiplex.The distribution of allele and genotype frequencies were determined to screen dangerous haplotype and physiological and biochemical indexes among the genotypes were compared in NGT,T2DM and T2DM with EH group.Results:1.In NGT,T2DM and T2DM with EH group,the genotype and allele frequencies of 3 SNP rs26770(G),rs4311394(G),rs359419(T)conformed to Hardy-Weinberg equilibrium and showed no significant difference(P>0.05)among every group or between man and woman.2.The frequency of the risk genotype GG of SNP rs26770(G)in T2DM is higher than in NGT group(17.4%,11.4%,P=0.009).In the analysis of the recessive model(GG:AA+GA),genotype GG in T2DM was 1.637 times(P=0.045,R=1.637,95%CI:1.04-2.55).3.The combined genotype frequencies AG-GG-CC of 3 SNP in T2DM was higher than in NGT group(3.7%>1.2%,P=0.045).4.Haplotype GAT showed positive correlations with susceptibility of T2DM(P=0.007,OR>1);Haplotype AAC and GGT showed negative correlations with susceptibility of T2DM(P<0.05,OR<1).5.The risk genotype GG of rs26770 showed high BMI and WHR(P<0.05),low level of HDL-C and PA(P=0.082).The polymorphism of rs4311394 and the rs35941 had no significant differences of physiological and biochemical indexes among every group(P>0.05).6.The alleles frequencies of of 3 SNPs in yanbian-korean populations had significant differences with that in HapMap database(ss44657212,ss7964718,ss48419060).The allele G frequency of rs26770 in yanbian-korean was significantly lower than European(CEU)(P<0.01)and higher than Japanese in Tokyo(JPT)(P<0.05),but no significant differences with Han Chinese in Beijing(HCB)and African(YRI)(P>0.05).The frequencies of the alleles G of rs4311394 was significantly higher than CEUandYRI(P<0.01)and had no differences with HCB and JPT(P>0.05).The alleles T frequencies of rs35941 that had no differences with HCB(P>0.05)was higher than CEU,YRI and JPT(P<0.01).Conclusions:1.The polymorphism of rs26770 is associated with susceptibility of T2DM in Yanbian Chinese-Korean population;2.The polymorphism of rs4311394 and rs35941 is not associated with susceptibility of T2DM in Yanbian Chinese-Korean population;3.The risk genotype GG of rs26770 that increased BMI and WHR,lowered HDL-C and PA showed recessive mode of inheritance;4.Haplotype GAT is a risk haplotype of T2DM in Yanbian Chinese-Korean population;5.The combined genotype AG-GG-CC of rs26770,rs4311394 and rs35941 increases the risk of developing T2DM;6.There is a racial difference in the polymorphisms of gene ARL15.