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Correlation Between ENOS, DDAH2 Gene Polymorphism And Plasma ADMA And NO Levels In Type 2 Diabetes Mellitus And Type 2 Diabetic Nephropathy In Han Population Of Yunnan

Posted on:2018-11-08Degree:MasterType:Thesis
Country:ChinaCandidate:R J DongFull Text:PDF
GTID:2354330518987008Subject:Internal medicine
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Objective: To investigate the relationship between eNOS gene 4a/b, 894G/T polymorphism, DDAH2 gene -1151A/C polymorphism and plasma ADMA, NO level and type 2 diabetes mellitus.Methods:Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was detected in 147 cases of healthy control group, 344 cases of type 2 diabetes mellitus group eNOS gene 894G/T,4a/b polymorphism and DDAH2 gene -1151A/C polymorphism, using enzyme-linked immunosorbent assay (ELISA) measured the level of plasma ADMA, the level of plasma NO by nitrate reductase method, the comparison between two groups of genotype, allele frequency distribution and related clinical indicators.Results: ?The frequency of aa+ab genotype and a allele in the 4a / b locus of the eNOS gene in the T2DM group were higher than in the NC group (?2=13.314, p<0.001; ?2=12.275, p<0.001);?The frequency of GT+TT genotype and T allele of the eNOS gene 894G/T in the T2DM group were higher than in the NC group (?2=6.221,p=0.012; ?2=6.397, p=0.011);?The frequency of CC genotype of DDAH2 gene -1151A / C in T2DM group was higher than in healthy control group (?2=6.241,p=0.043). There was no significant difference in frequency distribution between A and C allele (?2=3.149,p=0.061);? the level of plasma ADMA in T2DM group(1.19±0.44umol/L) was higher than that of the control group (0.60±33 umol/L),there were statistically significant differences between the two groups (P<0.01 );?the level of plasma NO in T2DM group (57.73±9.67umol/L)was lower than that of the control group (78.81 + 15.54 umol/L), there were statistically significant differences between the two groups (P<0.01);?Plasma ADMA levels was positively correlated with HOMA-IR, systolic blood pressure, diastolic blood pressure, low density lipoprotein and fasting blood glucose (r = 0.438,0.354,0.253,0.186,0.381, P <0.05). but it was negatively correlated with NO (r = -0.426, P <0.05); Plasma NO level was negatively correlated with systolic blood pressure, diastolic blood pressure, low density lipoprotein and ADMA (r = -0.318, -0.223, -0.163, -0.426, P <0.05); ?eNOS gene 4a/ b locus: the systolic blood pressure of aa + ab genotype carriers was significantly higher compared with bb genotype carriers (P <0.05); eNOS gene 894G/T locus: the plasma NO level of GT + TT genotype carriers was significantly lower than that of GG genotype carriers (P <0.05); DDAH2 gene -1151A / C-site: plasma low-density lipoprotein in CC genotype carriers was significantly increased compared with AC genotype carriers (P <0.05);(8) Logistic regression of the development of T2DM or not showed that the level of ADMA, age,eNOS gene 4a / b locus aa genotype,eNOS gene 894G/T locus GT genotype may be the risk factor for the development of T2DM (OR=14.170, 1.322, 22.441, 2.881), plasma NO and high Density lipoprotein may be a protective factor for the development of T2DM (OR = 0.883, 0.005).Conclusion: The polymorphism of eNOS gene 4a / b, 894G/T locus and DDAH2 gene-1151A / C locus were found in the Han population of Yunnan province; The aa genotype of eNOS gene 4a / b locus, the GT genotype of eNOS gene 894G / T locus in Yunnan Han population are the risk factors of type 2 diabetes mellitus ; the level of ADMA was higher than that of health the control group, the NO level is lower than the healthy control group,ADMA could be a risk factor of type 2 diabetes mellitus,NO may be a protective factor for type 2 diabetes mellitus.Objective: To investigate the relationship between eNOS gene 4a / b, 894G / T polymorphism, DDAH2 gene -1151A/C polymorphism and plasma ADM A, NO levels and type 2 diabetic nephropathy.Methods: a case-control study, The subjects were divided into healthy control group(NC group) 147 cases and case group (T2DM group) 344 cases, and on the basis of random urinary protein / creatinine ratio (UACR), the patients were divided into 202 cases of type 2 diabetes without nephropathy (DNO group), 79 cases of Type 2 diabetic patients with early nephropathy (group DN1), 63 casesof type 2 diabetes mellitus with clinical nephropathy (DN2 group),142 cases ofthe type 2 diabetic nephropathy group(DN1+DN2 group) ,the five groups between the genotype and allele frequency distribution and the related clinical indicators were compared.Results: ?The frequency of aa + ab genotype of the eNOS4a / b locus in DNO group,DN1 group, DN2 group and DN1+DN2 group was higher than NC group. The frequency of aa + ab genotype in DN2 group was higher than that in DN1. The frequency of aa + ab genotype in DN2 group?DN1 + DN2 group was significantly higher than that in DNO group (p <0.05). There was no significant difference between DN1 group and DNO group (p> 0.05); The frequency of a allele in DN2 group, DN1 group, DN2 group and DN1 + DN2 group was higher than that in DNO group (P<0.05).There was no significant difference between DN1 group, DNO group and DNI group(p>0.05).? The frequencies of GT + TT genotype of the eNOS 894G /T locus in DNO group, DN1 group, DN2 group and DN1+DN2 group were higher than those in healthy control group (p <0.05). There was no significant difference between DNOgroup,DN1 group,DN2 group,DN1 + DN2 group (p> 0.05). The frequencies of T allele frequencies of eNOS gene 894G / T in DNO group, DN1 group, DN2 group and DN1+ DN2 group were significantly higher than those in healthy control group (p < 0.05).The frequency of T allele in DN2 group and DNI + DN2 group was higher than that in DNO group (p <0.05). There was no significant difference between DN1 group, DN2 group and DN1 + DN2 group (P> 0.05)?The frequency of CC genotype in DDAH2 gene -1151A/C locus in DNO group, DN1 group, DN2 group and DN1 + DN2 group was higher than in healthy control group (p <0.05). There was no significant difference between DNOgroup, DN1 group, DN2 group, DN1 + DN2 group (P> 0.05). The frequency distribution of A and C alleles in DDAH2-1151A / C was not statistically significant (P> 0.05).?ADMA levels between groups: DN2 group >DN1 group > DNO group,DN1 + DN2> DNO group, after analysis of covariance,ADM A concentration in the differences between the 5 groups still have statistical significance (p < 0.05);?Each group NO level: DN2 group < DN1 group < DNO group, DN1 + DN2 group <DNO group, after analysis of covariance, the NO concentration in the differences between the 5 groups still have statistical significance (p < 0.05);?The levels of SBG and HOMA-IR in DN2 group, DN1 group and DN1 + DN2 group were higher than those in DNO group (P <0.05), and the levels of HbA1C in DN2 group, DN1 group and DN1 + DN2 group were higher than those in DNO group DN;? The logistic regression of development DN or not showed that systolic blood pressure, FBG,ADMA level?eNOS gene 4a / b locus aa genotype and eNOS gene 894G / T locus GT genotype may be the risk factor for the development of DN (OR = 1.042,1.236,9.938,33.033,1.099),The NO level may be a protective factor for the development of DN(OR = 0.916);The logistic regression of the progress of DN or not shows that systolic blood pressure may be a risk factor for the progress of DN (OR = 2.339), and NO may be a protective factor for the progress of DN (OR = 0.898).Conclusion:?The level of plasma NO in the Han population of Yunnan area may be the protective factor for the development and progress of DN.?The aa genotype of eNOS gene 4a / b locus, the GT genotype of eNOS gene 894G / T locus in Yunnan Han population are the risk factors for the development of DN;? plasma ADMA levels may be a risk factor for development DN,but no correlation with the progress of DN.
Keywords/Search Tags:Dimethylarginine-dimethylamine hydrolase gene2, endothelial nitric oxide synthase, Type 2 diabetes mellitus, Gene polymorphism, Type 2 diabetes mellitus nephropathy
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