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The Correlation Between Accumulative Effect ARL15,PGC-agene SNPs With Type 2 Diabetes Mellitus And Macroangiopathy In Chinese-koreans And Han In Yanbian

Posted on:2020-05-18Degree:MasterType:Thesis
Country:ChinaCandidate:W ShaoFull Text:PDF
GTID:2404330572977884Subject:Biochemistry and Molecular Biology
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Objective:To investigate the single nucleotide polymorphisms(SNPs)of ADP-ribosylation-like factor(ARL15)rs6450176 and peroxisome proliferator receptor y coactivator-la(PGC-la)rs7656250 in Chinese-Korean and Han populations in Yanbian area between type 2 diabetes(T2DM)with macrovascular disease(MA).Methods:A case-control design was used to collect 210 patients with normal glucose tolerance(NGT),185 patients with T2DM,and 186 patients with T2DM and MA(combined with MA).Genotyping and sequencing were performed using the single base extension method(SnaPshot(?)Multiplex);serum ARL15,insulin(INS)and adiponectin(PA)were detected by enzyme-linked immunosorbent assay(ELIS A);Collected the physiological and biochemical of the samples,including height,weight,hip circumference,waist circumference,body fat percentage and calculate the body waist-to-hip ratio(WHR).High-density lipoprotein(HDL-C),low-density lipoprotein(LDL-C),total cholesterol(TC),triglyceride(TG)and fasting blood glucose(FPG)were detected by biochemical detector;carotid intima-media thickness(IMT)and plaque were measured by color Doppler B-mode ultrasound.Result:1.Analysis of physiological and biochemical characteristics and three protein indexes of Chinese-Korean and Han nationalities:BMI,TG,FPG and body fat percentage of Korean and Han nationality were higher in T2DM group and combined MA group than in NGT group(p<0.01);The TC,MI level in the combined MA group was higher than that in the NGT group(p<0.05).The WHR in the Han group with the MA group was higher than that in the T2DM group and the NGT group.The difference was statistically significant p<0.001),but the INS level.There was no difference between the T2DM group,the combined MA group and the NGT group(p<0.05).The LDL-C level in the combined MA group was significantly higher than that in the NGT group(p<0.05).The WHR level in the combined MA group was significantly higher(p<0.05).Significantly higher than the NGT group and T2DM group,the difference was statistically significant(p<0.01);while the Korean ARL15 level in the T2DM group,combined with the MA group was higher than NGT,but no statistical significance(p>0.05),PA The HDL level was significantly lower in the T2DM group and the combined MA group than in the NGT group(p<0.01).The ARL15 level in the Han group was significantly higher than that in the N2 group in the T2DM group and the MA group.The difference was statistically significant(p<0.05),but the PA level was not significantly different from the NGT in the T2DM group and the combined MA group(p>0.05).2.Comparison of allele frequency and genotype frequency distribution:Allele frequencies and genotype frequencies of ARL15 and PGC-la SNPs(rs6450176,rs7656250)were consistent with Hardy-Weiberg in NGT group,T2MD group and combined MA group.(p>0.05),with group representative.Polymorphism analysis of ARL15 gene rs6450176 showed that there was no ethnic difference between the Korean and Han nationality in the NGT group(p>0.05).The frequency of carrying AA or AG genotype was significantly lower in the combined MA group.In the T2DM group,it was statistically significant(p=0.022,OR=0.581,95%CI:0.369-0.914),which was a dominant genetic feature.Compared with GG genotype,ARL15 rs6450176 carrying AG/AA genotype showed a decreasing trend compared with GG genotype,and the difference was statistically significant(p<0.05).In the T2DM group and the combined MA group,the AG/AA genotype was carried.The samples,PA and IR showed a decreasing trend compared with the samples carrying the GG genotype,the difference was statistically significant(p<0.05);the ARL15 level did not differ in each genotype.3.ARL15 rs6450176(A/G),PGC-1? rs7656250(C/T)combined genotype analysis:A total of 9 joint genotypes were found,and the frequency of carrying GG-CT combined genotypes was significantly greater in the combined MA group than in the T2DM group(p=0.008,OR=2.304,95%CI:1.258-4.219),which increased the risk of taking the combined MA by about 2.3 times;the frequency of carrying the AA-CC combined genotype was significantly lower in the combined MA group than in the NGT group(p=0.022,OR=0.248,95%CI:0.070-0.886),has a protective significance.4.Analysis of positive combined genotypes and indicators:(1)Individuals carrying AA-CC genotypes,WHR levels were present in combined MA group>T2DM group>NGT uptrend(p=0.038),while in group MA Significantly greater than the NGT group(p=0.019),the difference was statistically significant;TG,FPG,body fat percentage in the T2DM group and the combined MA group was significantly greater than the NGT group,the difference was statistically significant(p<0.05);BMI was significantly higher in the T2DM group than in the NGT group;The combined MA group was significantly lower than the NGT group,and the difference was statistically significant(p=0.017).(2)Samples carrying GG-CT combined genotype:WHR,FPG,and body fat percentage were higher in the T2DM group and the combined MA group than in the NGT group,the difference was statistically significant(p<0.05);TC and TG were combined.The MA group was significantly higher than the NGT group,the difference was statistically significant(p<0.05);the PA level was significantly lower in the T2DM group than in the NGT group,and significantly higher in the combined MA group than in the T2DM group,the difference was statistically significant(p<0.05);IR level T2DM group was significantly higher than NGT group(p=0.01).Conclusion:1.ARL15 gene rs6450176-A is a protective factor It's can delays the development of complication of T2DM patients with MA.It is a dominant inheritance pattern;the SNP allele frequency and genotype frequency are not ethnic differences between Chinese-Korean and Han nationality;ARL15 gene rs6450176 mutation Does not affect the ARL15 protein level changes.2.ARL15 gene rs6450176 and PGC-1? gene rs7656250 combined genotype GG-CT interaction effect increased ARL15 level,down-regulated PA and HDL levels,increased insulin resistance,induced dyslipidemia,and promoted T2DM with MA increased risk of 2.3 times,and AA-CC combined genotype delays the development of T2DM patients with combined MA;...
Keywords/Search Tags:ADP-ribosylation-like factor(ARL15),peroxisome proliferator receptor gamma coactivator 1?(PGC-1?), type 2 diabetes mellitus(T2DM), macrovascular disease(MA), mononuclear Glycosidic acid polymorphism(SNP)
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