Association Of DDAH2 Gene - 449G / C Polymorphism And ADMA Level With Type 2 Diabetes Mellitus And Type 2 Diabetes Mellitus Complicated With Atherosclerosis

[Objective] The aim of this study was to investigate the allele and genotype frequency distribution of DDAH2gene-449G/C locus polymorphism. Specifically, we wanted to evaluate the correlation of DDAH2gene-449G/C locus polymorphism and plasma ADMA levels with type2diabetes (T2DM) in the Han population of Yunnan Province.[Methods] DDAH2-449G/C locus polymorphism were genotyped in238T2DM cases and146normal controls by polymerase chain reaction-restricted fragment length polymorphism(PCR-RFLP). The plasma levels of ADMA were detected by enzyme linked immuno sorbent assay (ELISA). Genotype frequencies, allele frequencies and clinical indexes were compared among groups.[Results]①The G/G genotype and allele G of DDAH2gene were higher in type2diabetes than in normal controls (X2=16.052, p<0.001; X2=13.616, p<0.001);②In T2DM group, there was higher ADMA levers in G/G genotype, the difference had statistical significance (P<0.05). There was no correlation between DDAH2gene-449G/C locus polymorphism and HOMA-IR.(P>0.05);③The plasma ADMA levels was higher in T2DM group (9.51±2.44umol/L) than in NC group (4.79±0.68umol/L), and the difference has statistical significance after covariance analysis (P<0.05).④There was a positive correlation between plasma ADMA and total cholesterol (TC), low density lipoprotein (LDL), uric acid (UA), fasting blood glucose(FBG), postprandial blood glucose(PBG), systolic blood pressure(SBP) and diastolic blood pressure (DBP)(r=0.233、0296、0.169、0.224、0.198、0.348、0.380,P<0.05). There was no correlation between plasma ADMA and HOMA-IR (P>0.05). Multiple stepwise regression analysis showed that there was a remarkable correlation between plasma ADMA and fasting blood glucose (FBG).⑤Logistic regression analysis showed that DDAH2gene-449G/G genotype, plasma ADMA levels, LDL were independent determinants in T2DM patients (OR=5.6,28.650,24.559)[Conclusion]①The-449G/C of DDAH2gene exist polymorphisms in the Han population of Yunnan Province.②The DDAH2gene-449G/G genotype may be the risk factor of T2DM patients in the Han population of Yunnan Province and this genotype may carries higher ADMA levers.③The plasma ADMA levels was elevated in T2DM and it markedly associated with fasting plasma glucose (FBG).④There was no correlation between plasma ADMA or DDAH2gene-449G/C locus polymorphism and insulin resistance. [Objective] The aim of this study was to investigate the correlation of DDAH2-449G/C polymorphism and plasma ADMA levels with diabetic atherosclerosis in the Han population of Kunming.[Methods] A case-control study was applied. The lumen diameter, intima integrity and vascular elasticity of common carotid artery, arteries were examined by Aloka α10Doppler ultrasound and echo—tracking. Subjects consist of146normal controls,80T2DM unincorporated atherosclerosis cases (DO group),71early diabetic atherosclerosis patients (D1group),87middle-late diabetic atherosclerosis patients (D2group) and158diabetic atherosclerosis patients (D1+D2group). The genotype frequencies, allele frequencies and clinical index were compared among groups.[Results]①There was a significantly greater frequency of the G/G genotype and allele G of DDAH2gene in diabetic atherosclerosis group (D1+D2group) versus T2DM unincorporated atherosclerosis group (DO group)(p>0.05). But there were no significant differences in genotype or allele distributions according to polymorphism analyses among DO group versus NC group and D1group versus D2group (p>0.05).②In D1+D2group, plasma ADMA levels in G/G genotype was significantly higher than C/C+G/C genotype, the difference has statistical significance (P<0.05). There was no correlation between DDAH2gene-449G/C locus polymorphism and HOMA-IR.(P>0.05);③The ADMA levels among groups:D1+D2group> DO group; D2group> D1group> DO group. A statistically significant difference was revealed after performing covariance analysis on the data (p<0.01).④There was a positive correlation between plasma ADMA, common carotid arterial intima-media thickness and smoking index.(r=0.712,0.388, p<0.05); There was no correlation between plasma ADMA and HOMA-IR (p>0.05).⑤Logistic regression analyses showed that plasma ADMA levels was the independent determinants of the occurrence and development of diabetic atherosclerosis (OR=42.835,39.047). The G/G genotypes of DDAH2gene was the independent determinants in diabetic atherosclerosis patients.(OR=2.765).[Conclusions]①The G/G genotype of DDAH2gene may be associated with diabetic atherosclerosis in the Han population of Kunming.②The G/G genotype of DDAH2gene carries higher ADMA levers. There was a positive correlation between plasma ADMA, common carotid arterial intima-media thickness and smoking index.③The levels of plasma ADMA may be a reliable predictor of the occurrence and development of diabetic atherosclerosis.④There was no correlation between DDAH2gene-449G/C locus polymorphism or plasma ADMA and insulin resistance.