Association Between The 936C/T Polymorphism In The 3’-untranslated Region Of Vascular Endothelial Growth Factor Gene And Diabetic Peripheral Neuropathy In Type 2 Diabetes Mellitus

ObjectiveThe purpose of this study was to investigate the relationship between VEGF gene936C/T Single nucleotide polymorphism and clinical and biochemical indexes,and the relationship with diabetic peripheral neuropathy,thus providing a theoretical basis for the prevention and treatment of type 2 diabetes with diabetic peripheral neuropathy.Research subjectsAccording to WHO 1999 diabetes diagnosis and exclusion criteria^[45],during September 2015 to October 2017,388 patients with type 2 diabetes from the affiliated hospital of Shandong first Medical University and 240 healthy control subjects who routinely accepted physical examination in our hospital during the same period were included in this study.All subjects were asked to complete a self-reported questionnaire and provided an overnight fasting blood sample.The study was performed in accordance with the Declaration of Helsinki and was approved by the ethics committee of the hospital.Written informed consent was obtained from all subjects in advance.All subjects were divided into three groups,DM group（diabetes without neuropathy,retinopathy or nephropathy）,184 patients with an average age of 59.76±11.08 years and a history of8.49±4.19 years,94 men and 90 women.DPN group（diabetes with peripheral neuropathy only）,204 patients with an average age of 60.93±9.58 years and a history of 8.82±3.18 years,105 men and 99 women.NC group（normal control）,240 cases with an average age of 59.78±10.21 years,130 men and 110 women.Diagnostic criteria for diabetic peripheral homeopathy according to Liu[8]1.A clear history of diabetes,accompanied by autonomic symptoms such as pain,numbness,and chills,as well as a few symptoms related to weakness.Tendon reflexes in the limbs weaken or disappear.3.Sensory nerve conduction velocity（SNCV）<40 m/s,motor nerve condu-ction speed（MNCV）<45 m/s.Patients with Neuropathy caused by other reasons,subje ctescombined with severe disease of heart,liver and kidney,as well assubjects with lower extremity vascular blocking exceeding more than 50%were excluded from this study.MethodRestrictive fragment length metamorphism（RFLP）technology and polymerize chain reaction（PCR）are used to determine the genomic typing of all individuals.The clinical and biochemical parameters,plasma VEGF concentration and VEGF 936C/T single nucl-eoli polymorphous were statistically analyzed in different genotypes and groups.All calculations were performed using the SPSS 18.0 version for Windows.Chi-square analysis was used to test whether VEGF genotype distribution followed the Hardy-Weinberg equilibrium.The data were non-normally distributed and values are given as medians（interquartile range）.All other variables were presented as means±SD（x±s）.One-way analysis of variance（ANOVA）or Kruskal-Wallis test was used to compare continuous variables among groups.A Chi-square analysis was performed to compare noncontinuous variables among groups.Multiple regression analysis was used to estimate the relation-ship between DPN and other clinical characteristics.We measured the contribution of the polymorphism and interactive effects with other risk factors for type 2diabetic nephropathy using multiple Forward Conditional logistic regression analysis.Result:1.Frequency comparison of C allele and CC genotype:Type 2 diabetes combined with peripheral homeopathy（DPN group）compared to normal control group（NC group）（χ²=9.510 and 9.877,P<0.05）and simple diabetes（T2DM group）（χ²=5.218 and 5.615,P<0.05）The genotype frequency was significantly increased and there were statistical differ-rences.2)Comparison of the genotype（CT+TT）frequency and the frequency of the T allele carrying the T allele:Type 2 diabetes mellifluous combined with peripheral homeo-pathy（DPN group）compared to the normal control group（NC group）（χ2=9.315 and9.522,P<0.05）and simple diabetes group（T2DM group）χ2=5.345 and 5.185,P<0.05)signific-antly reduced.2.Multiple risk factor analysis showed that.1)serum LDC-c,total cholesterol（TC）,Hb A1c levels,and plasma vascular endothelial growth factor（VEGF）concentrations were positively correlated with type 2 diabetic peripheral homeopathy.2)Vascular epithelial growth factor 3’-UTR region 936C→T monoxide metamorphism is negatively related to the risk of peripheral Neuropathy in type 2 diabetes（β=-1.035,OR=0.378,P=0.006,CI:0.159-0.812）.Conclusion:There exists 936C→T single nucleotide polymorphism located in the 3’-untraslated region of VEGF in individuals of Han nationality from Shandong Province.Among them,the T T allele and the T allele carryinggenotypes（936 TT genotype and 936 CT genotype）may be related to the reduced risk of diabetic peripheral homeopathy,While the C allele and the C allele carryinggenotypes CC genotype may be genetic markers of peripheral homeopathy in patients with type 2 diabetes.