Relationship Between The Plasma Homocysteine Levels And The Polymorphisms Of Its Metabolis Enzymes And The Diabetic Nephropathy

Objective To investigate the relationship of gene mutations of methylenetetrahydrofolate reductase(MTHFR)C677T,cystathionineβ-synthase(CBS)T27796C,methionine synthase (MS)A2756G,methionine synthase reductase(MSR)A66G and plasma homocysteine levels in type 2 diabetics with diabetic nephropathy(DN).To explore the influence of genetic factors on plasma homocysteine levels and the significance of genetic factors in the development of diabetic nephropathy.Methods There were no obvious differences in age and sex amony the three groups.The plasma homocysteine levels of 35 type 2 diabetics without diabetic nephropathy(DM),48 diabetic nephropathy(DN)and 27 healthy controls(CON)measured using hype-performance liquid chromatography with fluorescence detection.Moreover,the polymorphisms of MTHFR genetic C677T,CBS genetic T27796C,MS genetic A2756G and MSR genetic A66G were determined by polymerase chain reaction-restriction fragment length polrmorphism(PCR-RFLP) in three groups.Measurement data was expressed with mean±standard deviation((?)±s).The comparison of measurement data was adopted with T Test and analysis of variance.The distribution of genetype and allele frequencies was adopted with Chi-Square Test.Bivariate Correlation was expressed with Spearman Correlation.The risk factors for diabetic nephropathy were selected with Logistic Regression.Statistical analysis use the SPSS 11.5 software.Results The plasma homocysteine levels were(20.49±13.31)μmol/L in patients with type 2 diabetic nephropathy,significantly higher than those in healthy controls(11.90±14.34)μmol/L, P＜0.05,and that also significantly higher than those without renal complications(13.10±8.70)μmol/L,P＜0.05.The frequencies of MTHFR TT homogenetic type and allele T(56.3%,72.0%)in type 2 diabetic with DN were significantly higher than those in type 2 diabetic without DN(22.9%,36.0%)or the healthy controls(14.8%,35.0%).There were significantly differences in the frequencies of MTHFR mutations among three groups(P＜0.05).The plasma homocysteine levels in patients with MTHFR TT genotype were markerly higher than those in patients with MTHFR CC genotype[(25.69±12.48vs.13.55±5.49)μmol/L,P＜0.01].There were no significantly differences in the frequencies of CBS mutations among three groups(P＞0.05).The plasma homocysteine levels in patients with CBS CC genotype were markerly higher than those in patients with CBS TC genotype[(25.69±12.48)vs.(14.22±6.24)μmol/L,P＜0.001],and CBS TT genotype[(25.69±12.48)vs.(13.55±5.49)μmol/L,P＜0.001].There were no significant differences in the frequencies of MS mutations among three groups,and there were no significant differences in plasma Hcy levels between AG genotype and AA genotype of MS. There were no significant differences in the frequencies of MSR mutations among three groups,but there were differences in plasma homocysteine levels between AG genotype and AA genotype of MSR.Spearman Correlation analysis showed that the genotype of MTHFR C677T,CBS T27796C and MSR A66G were the influence factors of the plasma homocysteine levels.Logistic Regression analysis showed that the plasma homocysteine levels and the genotype of MTHFR C677T were risk factors for diabetic nephropathy.Conclusion The plasma homocysteine levels might be associated with diabetic nephropathy. MTHFR TT homogenetic type,CBS CC homogenetic type,and MSR AG genotype can raise the plasma homocysteine levels.MTHFR gene C677T mutations associated with a predisposition to increase of plasma homocysteine may represent a genetic risk factor for diabetic nephropathy in type 2 diabetic mellitus.