Correlation Between The Three-yin And Three-yang Physique And ApoE Gene Polymorphism In Diabetic Peripheral Neuropathy

BackgroundMost diseases are the result of the combination of genetic and environmental factors.Different genetic backgrounds make the disease have different incidence and clinical manifestations among different ethnic groups,different sexes and other groups,and also make differences in the susceptibility of different populations to a certain disease.The Physique Theory of traditional Chinese medicine believes that the state of constitution determines whether the disease is sick or not and the tendency of the disease.At the same time,physique also has an important influence on the type of disease,the disease,the position of the disease,the stage of the disease and the tendency of the disease.Therefore,some scholars believe that we can explain the mechanism of physical fitness and disease susceptibility from the perspective of disease related gene phenotypes.The treatment effect of diabetic peripheral neuropathy is not satisfactory.Using the combination of traditional Chinese and Western medicine,looking for laws from the perspective of physical characteristics and genetic polymorphisms,exploring the susceptible genes of different physiques and syndromes of diabetic peripheral neuropathy in Chinese medicine,the exploration of genes will help to reveal the connotation of TCM syndrome and provide more accurate information for clinical diagnosis and treatment.Objective1.To study the relationship between Apo lipoprotein E(ApoE)gene polymorphism and type 2 diabetic peripheral neuropathy,To study the mechanism of ApoE gene polymorphism on diabetic peripheral neuropathy.2.Analyze the distribution and syndrome characteristics of TCM in patients with type 2 diabetes mellitus and peripheral neuropathy.To discuss the correlation between constitution and syndrome,constitution and distribution of ApoE gene,in order to provide molecular biological basis for diabetic peripheral neuropathy in TCM differentiation of constitution,disease differentiation and syndrome differentiation.Methods355 type 2 diabetes mellitus patients(215 with peripheral neuropathy,140 without peripheral neuropathy and their causes are 10years or longer)and 159 non-diabetic controls.1.Association between ApoE gene polymorphism and diabetic peripheral neuropathy(1)The clinical index of the selected population was detected,and the blood samples were extracted,the target gene amplification and direct sequencing were used to detect the genotype of ApoE gene.(2)The distribution of ApoE genotype and allele in three groups was statistically analyzed.(3)Electromyography and vascular ultrasound were used to detect type 2 diabetic peripheral neuropathy andNon peripheral neuropathy group.Groups based on whether or not they are associated with atherosclerosis,compare the distribution of ApoE genotype and allele in each group.Compare the motor nerve conduction velocity and sensory nerve conduction velocity in each group.2.Correlation between three Yin and three Yang constitutions,TCM syndrome and ApoE gene polymorphism in diabetic peripheral neuropathy(1)Based on Professor Zhao Jinxi's theory of three Yin and three Yang constitutions.The"three in and three Yang constitution scale" is adopted in the study of Dr.Gong Qing.To investigate the constitutions distribution of three Yin and three Yang in normal population of type 2 diabetic peripheral neuropathy and normal glucose metabolism.(2)According to the "diabetes and its complications of the virtual standard diagnostic criteria." Which issued by World Federation of traditional Chinese Medicine Association Diabetes Specialized Committee in 2016,the patients who met the above criteria were analyzed statistically.Analyze the distribution of physical fitness and the results of clinical tests among different constitutions.To study the correlation between three yin and three Yang constitutions and TCM Syndrome Types in diabetic peripheral neuropathy patients.To study the correlation between constitution and ApoE gene polymorphism in diabetic peripheral neuropathy patients.Results1.Association between ApoE gene polymorphism and diabetic peripheral neuropathy(1)The frequencies of E4/X genotype(Including genotypic E3/E4 and E4/E4)in DPN(28.9%)were higher than those in T2DM(15.2%)or NC group(18.9%).The difference was statistically significant(P=0.003,P=0.026).The frequencies of E4 allele(15.7%)in DPN group were higher than those in T2DM group(8.9%)or NC group(9.7%).The difference was statistically significant(P= 0.010,P= 0.019).(2)In group DPN,compared with group NC,E4/X genotype carriers had higher DPN risk than E3/E3 genotype(OR=1.821,95%CI 1.092?3.038,P=0.022),E4 allele carriers had a higher risk of DPN than E3 allele carriers(OR=1.738,95%CI 1.102?2.743,P=0.017)?In group DPN,compared with group T2DM,E4/X genotype carriers had higher DPN risk than E3/E3 genotype(OR=2.374,95%CI 1.348?4.181,P=0.003),E4 allele carriers had a higher risk of DPN than E3 allele carriers(OR=1.906,95%CI 1.168?3.110,P=0.010)?(3)There were significant differences in TC,LDL-C and ApoB among the three gene groups of E2/X,E3/E3 and E4/X in DPN groups.The levels of TC,LDL-C and ApoB in E4/X gene group were significantly higher than those in E2/X gene,Differences are statistically significant.There were significant differences in TG,HDL-C and ApoB among the three gene groups of E2/X,E3/E3 and E4/X in DM groups.The levels of TG,and ApoB in E4/X gene group were significantly higher than those in E2/X gene group,the levels of HDL-C in E4/X gene group were significantly higher than those in E2/X gene and E3/E3 group,and Differences are statistically significant.(4)Logistic regression analysis showed that HbA1c?ApoB?TC?The ApoE genotype are the risk factors for the occurrence of DPN(P<0.05)?HDL-C is a protective factor for the occurrence of DPN.(5)The above patients were further divided into four groups according to the results of Doppler ultrasound examination of lower extremity artery:Group A:type 2 diabetes group(without peripheral neuropathy,without atherosclerosis),33 cases.Group B:Type 2 diabetes mellitus complicated with atherosclerosis(without peripheral neuropathy)in 107 cases.Group C:type 2 diabetic peripheral neuropathy(without atherosclerosis),30 cases.Group D:type 2 diabetes mellitus with peripheral neuropathy and arteriosclerosis group,185 cases.The difference of atherosclerotic lesion between diabetic peripheral neuropathy group and non-diabetic peripheral neuropathy group was statistically significant.(6)There was no significant difference in age,course of disease,BMI and HCY between A group and B group in the two groups.The HDL-C in group B was lower than that in group A,and the difference was statistically significant.There was no significant difference in the difference of LDL-C and TG between the two groups.(7)There was no significant difference in age,course of disease,BMI and HCY between C group and D group in the two groups.The TC in group D was higher than that in group C,and the difference was statistically significant.The HDL-C in group D was lower than that in group C,and the difference was statistically significant.There was no significant difference in the difference of LDL-C and TG between the two groups.(8)The combined atherosclerosis group(B+D)was compared with that of the non-atherosclerosis group(A+C),The difference in genotype frequency is statistically significant(P=0.033).The ApoE4 genotype frequency of group B+D(25.8%)was higher than that of group A+C(12.9%),and the ApoE4 genotype frequency was statistically significant(P=0.030).(9)The motor nerve conduction velocity(MCV)were different in median nerve?tibia nerve and ulnar nerve.The motor nerve conduction velocity in group B was slower than that in group A.Median nerve conduction velocity and tibia nerve conduction velocity difference were statistically significant(P<0.05).The motor nerve conduction velocity in group D was slower than that in group C,and there was a significant difference in tibia nerve conduction velocity(P<0.05).(10)The Sensory nerve conduction velocity(SCV)were different in median nerve?tibia nerve and Peroneus nerve.The sensory nerve conduction velocity in group B was slower than that in group A.Peroneus nerve conduction velocity difference were statistically significant(P<0.05).The sensory nerve conduction velocity in group D was slower than that in group C,and there was a significant difference in median nerve and Peroneus nerve conduction velocity(P<0.05).2.Correlation between three Yin and three Yang constitution,TCM syndrome and ApoE gene polymorphism in diabetic peripheral neuropathy(1)There were 210 cases of single constitution in diabetic peripheral neuropathy group.There was significant difference between the two groups according to the frequency of physical types.There were significant differences between the two groups in the constitution of the sun,the constitution of yin and the frequency of Tai Yin.In group NC,the constitution of the sun is more than that of group DPN,and the Tai Yin constitution and Shao Yin in group DPN are more than those in group NC.(2)Logistic Regression analysis showed that Phlegm dampness,Yang deficiency and dampness syndrome are positively correlated with Tai Yin constitution.(3)Logistic Regression analysis showed that Yang deficiency syndrome is positively related to the physique of less Yin(B=0.783,OR=2.187).(4)Compared with group NC,the risk of E4/X genotype in DPN group was 2.874 times higher than that in E3/E3 group.The risk of E4/X genotype in Tai Yin is 3.017 times the risk of E2/X genotype.Compared with group NC,the risk of E4 allele in group DPN is 2.313 times that of E3 allele,and the risk of E4 allele is 3.194 times that of E2 allele.Conclusion(1)ApoE gene polymorphism may be associated with type 2 diabetic peripheral neuropathy.The frequency of allele E4 and E3/E4 frequency in DPN group were significantly higher than those in DM group and NC group.Allele E4 may be associated with type 2 diabetic peripheral neuropathy.Type 2 diabetic patients with E4 allele are more likely to have peripheral neuropathy.(2)The physique of Tai Yin and the physique of Shao Yin are the susceptible constitution of DPN.People with diabetic peripheral neuropathy in Tai Yin constitution are prone to appear phlegm dampness syndrome,blood deficiency syndrome and water wet syndrome.People with diabetes mellitus and peripheral neuropathy with Yin deficiency constitution are prone to Yang deficiency syndrome.The mutation of ApoE locus,E4 allele and E4/X genotype increased the risk of DPN in Tai Yin constitution group.The detection of gene polymorphism is the key technology of this study.The exploration of the correlation between the identification of TCM Constitution and genetic polymorphism is the innovation of this research.