Relationship Between Serum Homocysteine Level,Methylenetetrahydrofolate Reductase Gene Polymorphism And Type 2 Diabetic Peripheral Neuropathy

Objective:This study was to investigate the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T gene polymorphism,serum homocysteine(Hcy)level and type 2 diabetic peripheral neuropathy(DPN).It has important guiding significance for further revealing the risk predictive value of serum Hcy level in DPN and the molecular mechanism of DPN.Methods:From June 2020 to December 2020,109 adult patients with type 2 diabetes who were hospitalized in Second Affiliated Hospital of Nanchang University were selected as the research objects.,the course of diabetes was more than 5 years.According to whether the patients with type 2 diabetes were complicated with diabetic peripheral neuropathy(DPN),the patients were divided into two groups:type 2 diabetic peripheral neuropathy group(DPN group,n=62)and non-diabetic peripheral neuropathy group(NDPN group,n=47).For all subjects in the two groups:(1)Collect general information:age,gender,duration of diabetes,height,weight,body mass index(BMI);(2)Blood test:serum Hcy level,folate concentration,Hb A1c,total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C),fasting blood glucose(FBG)and fasting C-peptide;(3)MTHFR gene polymorphism was detected by restriction fragment length polymorphism polymerase chain reaction(PCR-RFLP).T test,chi square test and multivariate logistic regression analysis were used to analyze the relationship between each variable and type 2 diabetic peripheral neuropathy,with P<0.05 as the standard of statistical differences.Results:(1)The general situation of all the subjects was compared,there was no significant difference in age,gender,height,weight,duration of diabetes and BMI between DPN group and NDPN group(all P>0.05).(2)Comparison of blood biochemical indexes between the two groups,there was no significant difference in Hb A1c,total cholesterol,triglyceride,low density lipoprotein,high density lipoprotein,fasting blood glucose and fasting C-peptide between DPN group and NDPN group(all P>0.05).There was significant difference in plasma Hcy level between DPN group and NDPN group(P<0.001).(3)Relationship between serum Hcy level and type 2 diabetic peripheral neuropathy:(1)The serum Hcy level in DPN group(18.81±7.58μmol/L)was significantly higher than that in NDPN group(12.06±4.18μmol/L)(P<0.001).(2)The abnormal rate of serum Hcy in DPN group(66.13%)was significantly higher than that in NDPN group(21.28%)(P<0.001).(3)According to MTHFR genotypes,we found that:When the genotype was CC,the serum Hcy level in DPN group(15.57±6.37μmol/L)was significantly higher than that in NDPN group(11.06±4.01μmol/L)(P<0.05).When the genotype was TT,the serum Hcy level in DPN group(23.28±8.24μmol/L)was significantly higher than that in NDPN group(13.57±4.47μmol/L)(P<0.05).When the genotype was CT,there was no significant difference in serum Hcy level between DPN group(17.07±6.07μmol/L)and NDPN group(13.00±4.23μmol/L)(P>0.05).(4)Relationship between MTHFR C677T gene polymorphism and type 2diabetic peripheral neuropathy:(1)The genotypes of MTHFR C677T in DPN group(CC:24.19%,CT:41.94%,TT:33.87%)and NDPN group(CC:51.06%,CT:40.43%,TT:8.57%)were significantly different(χ~2=12.906,P=0.002).(2)There was also significant difference in allele composition between DPN group(C:45.16%,T:54.84%)and NDPN group(C:71.28%,T:28.72%)(χ~2=14.831,P<0.001).(3)When serum Hcy level was normal,there was no difference in allele composition between DPN group(C:71.79%,T:28.21%)and NDPN group(C:61.90%,T:38.10%)(χ~2=1.234,P=0.267);when serum Hcy level was abnormally high,there was a significant difference in allele composition between DPN group(C:36.59%,T:63.41%)and NDPN group(C:68.75%,T:31.25%)(χ~2=5.692,P=0.017).(5)The joint effect of MTHFR C677T gene and Hcy level on type 2 diabetic neuropathy,Multiple logistic regression analysis showed that:(1)The effect of genotype on DPN was as follows:CC genotype compared with TT genotype,the or value was 0.125;CT genotype compared with TT genotype,the or value was 0.215,the TT genotype of MTHFR C677T may increase the risk of DPN(P<0.05).(2)Serum Hcy level is positively correlated with DPN,which is a risk factor for DPN(OR=1.132,95%CI:1.065～1.204).The higher the serum Hcy level,the higher the risk of DPN.Every 1μmol/L increase in serum Hcy level,the risk of DPN increased1.132 times.Conclusion:(1)Compared with the NDPN group,the DPN group was more stable,the serum Hcy level and abnormal rate were increased,after stratified by MTHFR C677T genotype,this phenomenon still existed;multivariate analysis also suggested that elevated serum Hcy was a risk factor for DPN.(2)Univariate and multivariate analysis showed that the genotype composition of MTHFR C677T is related to the occurrence of DPN,and TT genotype may be a risk factor for DPN.(3)Only when the serum Hcy level increased,allele T may be a risk factor for DPN.