| Objective:The study aimed at investigating the association between the single nucleo-tide polymorphisms(SNPs)of the gene ADP-ribosylation-like factor 15(ARL15),peroxisome proliferator-activated receptor-gamma coactivator 1 alpha(PGC-1?),transcription facor 7-like 2(TCF7L2)accumulative effectandwith type 2 diabetes mellitus(T2DM)and macroangiopathy in Korean and Han ethnic nationality of Yanbian area in China.Methods:This was a case-control study including 96 T2DM patients,160 T2DM with macroangiopathy patients and 168 controls.SNP tying and sequencing are done by LDR and SnaPshot(?)Multiplex;Enzyme-linked immunosorbent assay(ELISA)was carried to detect the protein expression of Q9NXU5(ARL15),insulin(INS),Plasma Adiponectin(PA)and TCF-4(TCF7L2);Physiological and biochemical indexes were collected to calculate body mass index(BMI)and waist-to-hip ratio(WHR);For the measurement of carotid IMT and atherosclerosis plaque by using color ultrasonic apparatus.Using Hardy-Weinberg's law of equilibrium,the group representative of the study sample is determined.The analysis of covariance was used for several indicators of age influence sample statistics.Results:l.Genotype and allele frequency:ARL15,PGC-1? and TCF7L2 of the Korean and han nationalities have three SNPs,and there is no significant difference in the genotype and allen frequency of the three SNPs.The C allen frequency for PGC-1? gene rs7656250 in MA group(0.422)allele frequency was significantly higher than that of NGT group(0.377),and the difference was statistically significant(p=0.012,OR=1.499,%95CI=1.091-2.061).MA genotype frequency is greater than NGT group,the difference was statistically significant(p=0.019),carry rs7656250 polymorphism of the CC/CT genotype sample MA group had a significantly higher frequency,NGT group were statistically significant,to 1.9 times higher risk of T2DM with MA(p=0.005,OR=0.005,95%CI= 1.210?2.97),and has the characteristics of dominant inheritance pattem.The alleles and genotypes of the ARL15 and TCF7L2 genes(rs255758,rs7903146)had no significant difference between the NGT group and the T2DM group,the NGT group and the MA group and the T2DM group and the MA group(p>0.005).2.Control analysis of clinical indicators:there was a significant difference between the Korean and han nationality in the NGT group in the NGT group(p<0.005),only the BMI,FPG,INS and IR were detected in the NGT group.The Scr level was related to gender,and the results showed that the Scr level of the T2DM group and the MA group was significantly lower than that of the NGT group(p<0.005).In all samples,T2DM group and MA group were significantly higher than NGT group(p<0.005).ARL15 protein level T2DM group and MA group were significantly higher than the NGT group(p=0.023,p=0.001),and the MA group was significantly higher than the T2DM group(p=0.023).The WHR value MA group was significantly higher than that of NGT group(p=0.001),and the WHR value of T2DM group was higher than that of NGT group,but there was no statistical significance(p=0.116).There was no significant difference in TG,HDL-C,LDL-C,BUN,UA and TCF7L2(p>0.005).3.The three genes combined with testing all index case-control analysis:(1)The results showed that by the joint action of three genes carry:the MA group with AA-CT-CC combined genotype was significantly larger than that of NGT group(p=0.041,OR=1.660,95%CI:1.031-2.672),increasing the risk of T2DM combined with MA by about 1.7 times.The MA group with ac-tt-cc combined genotype was significantly less than the NGT group(p=0.019,OR=0.368,95%CI:0.158-0.858),which reduced the risk of T2DM combined with MA.(2)ARL15 gene and testing all index analysis:bring AA/AC genotype samples of T2DM group,MA group ARL15,PA,degree of IR,TC,TG,LDL-C,Scr,BUN,there were significant difference.the ARL15 level of T2DM and MA group were significantly higher than that of NGT group,ARL15 level between the three groups showed a trend of increasing,NGT<T2DM<MA(36.540±5.958<39.210±8.790<8.790±16.509)(p=0.001,p=0.001)/35.820±5.333<40.23±8.777<40.940±10.580(p=0.032,p=0.009);The PA level of the MA group and T2DM group was significantly lower than that in the NGT group,and the MA group<T2DM group<NGT group,which was 15.98±7.212<16.330±7.76<16.870±13.310(p=0.001,p=0.001)/16.720±7.471<17.250±7.641<17.710±12.214(p=0.038 p=0.014);In T2DM group and MA group,IR gradually increased:T2DM>MA>NGT:58.030±34.244>57.430±30.821>31.650±16.655(p=0.001,p=0.001)/59.470±30.053>51.010±24.564>29.010±11.8(p=0.001,p=0.001);The TC and TG levels in the T2DM group with AC gene were significantly higher than that in the NGT group(p=0.042,p=0.038),the BUN level of MA group was significantly higher than that of NGT group(p=0.034),and the TG level of MA group was significantly higher than that of T2DM group(p=0.043).(3)PGC-la gene and testing all index analysis:carry the CC genotype samples of T2DM group,MA group had a significantly higher levels of FPG NGT group(p=0.001,p=0.001),PA level of T2DM group and MA groups were significantly lower than NGT group(p=0.043,p=0.009),TG level of T2DM group was significantly higher than NGT group(p=0.029).TCF7L2 level of T2DM group was significantly lo,wer than NGT group(p=0.010).The levels of FPG,BUN and IR in T2DM group and MA group with CT genotype samples were significantly higher than that in NGT group(p<0.005),and the PA level of T2DM group and MA group was significantly lower than that of NGT group(p=0.008,p=0.001),the BMI level of T2DM group was significantly higher than that of NGT group(p=0.031),and the TC level of MA group was significantly higher than that of NGT group(p=0.013).Carry TT genotype sample cases of T2DM group and MA group of FPG,TC,ARL15 and IR were significantly higher than in NGT group(p<0.005),Scr of T2DM group and MA group were significantly lower than NGT group(p=0.001,p=0.001),the LDL-C and PA levels in T2DM group were significantly higher than that in the NGT group(p=0.0355,p=0.015),the BUN of MA group was significantly higher than that of NGT group(p=0.018),and the PA of MA group was significantly lower than that of NGT group(p=0.001).(4)TCF7L2 gene and the detection of all indicators:The CC and TC genotype with TCF7L2 gene were not correlated with the protein level of TCF7L2(p>0.005).These two genotypes were not associated with ARL15,INS,PA protein levels,and various physiological and biochemical indicators(p>0.005).(5)Comparison of positive and clinical indicators:the FPG and IR levels of the T2DM group and the MA group with AA-CT-CC combined genotype were significantly higher than that in the NGT group(p<0.005).The levels of TC and LDL-C in MA group were significantly higher than that in NGT group(p<0.005).The PA level of MA group was significantly lower than that of NGT group(p=0.002).(6)Correlation analysis:ARL15 was correlated with INS,IR and TCF7L2(p<0.001,7<0.005);There was correlation between INS and ARL15,PA and IR(p<0.01,p<0.05).IR was correlated with ARL15,INS and TCF7L2(p<0.001,p<0.0005).Conclusions:1.The ARL15,PGC-la,TCF7L2 genes(rs255758,rs7656250,rs7903146)are combined with AA-CT-CC interaction effect up-regulated the level of ARL15,lowered the PA level,induced dyslipidemia(TC/LDL-C increase,etc.),resulting in increased insulin resistance and 1.7 times increased risk of T2DM combined with MA.2.The C allen frequency for PGC-1? gene rs7656250 is highly correlated with T2DM and MA in Yanbian area,and it is performance as dominant mode3.There was no signifiant correlation between TCF7L2 gene rs7903146 polymorphism witn T2DM and MA,and the polymorphisms of rs7903146 of TCF7L2 gene were not associated with the protein expression of TCF7L2. |
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