| ObjectivesDiabetic nephropathy(DN)is a type 2 diabetes(T2DM)common and serious vascular complications,its development is closely related to genetic factors.Studies have shown that methyltetrahydrofolate reductase(MTHFR)genes are associated with vascular disease,and C677T and A1298C are common polymorphisms in MTHFR encoding genes.The purpose of this study was to assess whether the MTHFR gene C677T and A1298C polymorphisms were risk factors for DN in T2DM patients of Han nationality in Suzhou region,and to analyze the metabolic status of mutant MTHFR,providing reliable theoretical basis for screening the high-risk population of DN and early intervention treatment,so as to prolong the survival time of diabetic patients and improve the quality of life.Methods:According to the WHO diagnostic and typing criteria of diabetes,161 cases of T2DM patients treated from March 2017 to May 2018 were selected,including 81 cases of diabetic nephropathy group(DN)and 80 cases of diabetic without nephropathy group(DM).And the control group(NC)was established for 77 cases.All the subjects were Han people in Suzhou and were unrelated to each other.Peripheral blood samples were collected and related clinical data were collected.TaqMan genotyping technique was used to detect single nucleotide polymorphism(SNP)of the MTFHR gene C677T and A1298C,and the clinical indexes including blood glucose,blood lipids,homocysteine(HCY)and folate(FOL)were measured.SPSS 22.0 statistical software was used for data analysis and processing.Chi-square test was used for comparison of genotype and allele frequency,anova was used for comparison of multi-group mean,Logistic regression was used for relative risk assessment,and Pearson correlation was used for bivariate analysis.Results:1.The results of general clinical data analysis showed that there was no significant difference in age,height,weight,DBP,TC,HDL and LDL(P>0.05).BMI,SBP,TG,BUN,Cr,Cys-C and RBP of the DN group were significantly higher than that of the DM group and the NC group,with statistically significant differences(P<0.05).FBG and HbA1C of the DN group and the DM group were significantly higher than that of the NC group,and the difference was statistically significant(P<0.05).2.MTHFR gene distribution:(1)C677T polymorphism:the distribution frequency of 677TT in the DN group(25.9%)was significantly higher than that in the the DM group(11.2%)and NC group(10.4%),and the χ2 value was 10.522 and 9.827 respectively,P<0.05..The 677T allele frequency(51.2%)of DN group was significantly higher than that of DM group(33.1%)and NC group(33.8%),and the χ2 value was 10.821 and 9.845 respectively,P<0.05.(2)A1298C polymorphism:There was no statistical difference between the clinical groups of all genotypes(χ2＝1.334,P=0.856).No significant difference was found in 1298C allele fquenrecies(χ2=1.269,P=0.530).3.The combined analysis between MTHFR C677T and A1298C polymorphisms did not find the existence of 677TT/1298AC,677TT/1298CC and 677CT/1298CC.The frequency of 677CT/1298AC(25.9%)and 677TT/1298AA(22.8%)in the DN group was significantly higher than that in the DM group(l 1.2%and 12.5%)and NC group(10.4%and 11.7%)(P<0.05).4.Logistic regression analysis of MTHFR gene and DN:The risk of DN in C677T polymorphisms was 2.220 times of that carrying CC type(P=0.029,95%CI=1.085-4.541)and 4.421 times(P=0.002,95%CI=1.695-11.529).The risk of DN in T2MD patients with 677T allele was 2.670 times than that of non-677Tcarriers(P=0.004,95%CI=1.357-5.254),indicating that the 677T allele was a risk factor for DN.However,there was no significant correlation between the 1298C allele and DN(P>0.05).5.Comparison of the levels of HCY and FOL:(1)The DN group(19.76±7.81μmol/l)was significantly higher than that of the DM group(15.62±5.01μmol/l)and that of the NC group(8.09±3.74μmol/l).The average HCY level of the 677TT genotype(20.85±7.65μmol/l)was significantly higher than that of the other two genotypes,and the average HCY level of the 677CT genotype(15.07±7.57μmol/l)was also significantly higher than that of the 677CC genotype(11.29±5.28μmol/l).The average HCY level(17.64±7.05μmol/l)of double heterozygote(677CT/1298AC)was was higher than that of single heterozygote(677CT/1298AA and 677CC/1298AC).The differences were statistically significant The serum FOL of DN group(12.18±3.01 ng/ml)was significantly lower than that of DM group(13.50±2.71ng/ml)and NC group(15.43±2.95ng/ml),while that of DM group was also significantly lower than that of NC group.The average FOL level of the 677TT genotype(10.79±2.61ng/ml)was significantly lower than that of the other two genotypes,and the 677CT genotype(13.82±3.27ng/ml)was significantly lower than that of the 677CC genotype(14.74±2.47ng/ml).The average FOL level of double heterozygote 677CT/1298AC(12.0913.27ng/ml)was lower than that of single heterozygote 677CT/1298AA and 677CC/1298AC.The differences were statistically significant(P<0.05).6.There was a significant negative correlation between serum HCY and FOL(Pearson=-0.433,P<0.001),and the coefficient 187.Conclusion:1.The polymorphism of the MTHFR gene C677T is correlated with the occurrence of DN in Han population in Suzhou.The 677T allele is a risk factor for DN in T2MD patients.2.The polymorphisms of the MTHFR gene A1298C were not correlated with the incidence of DN,but it may have a synergistic effect with the mutation of C677T.3.MTHFR gene mutation is an important factor influencing the increase of HCY in plasma,and FOL level is negatively correlated with HCY. |
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