Analysis Of Risk Factors Of Diabetic Microangiopathy Based On TCM Syndrome And Preliminary Study Of Susceptibility Genes Of Diabetic Retinopathy

Object:Analyse related data,clinical symptom,TCM syndrome and laboratory examination of diabetic patient,to find more risk factors of diabetic microangiopathy.On this basis,after matching risk factors for diabetic retinopathy patients,screening patients with independent susceptibility genes,To provide basis for prevention and treatment of microangiopathy in type 2 diabetes mellitus and further study of diabetic retinopathy in future.Methods:(1)Used-made questionnaire,information of T2DM patients was collected on endocrine clinics and in-patient department from 13 hospitals such as Beijing,Shijiazhuang and Baoding between March 2016 and January 2017,cross sectional analysis was performed.Logistic regression analysis was used to univariate analysis and multivariate analysis.(2)On the basis of the risk factors of DR in the prophase,DR patients with all risk factors for DR were matched with information about T2DM patients without DR(includ general information,clinlcal symptom and laboratory examination).Completely consistent information was selected from DR and non DR patients as a pair,and included in the study.The whole blood was taken from the patient vein,Illumina human SNP typing chip technology was adopted,242901 SNP locus were screened for DR patients,identify all differential locus that all enrolled groups were present,genes with differential locus were searched by NCBI database(http://www.ncbi.nlm.nih.gov/),UCSC database(http://genome.ucsc.edu/),lncRNASNP database(http://bioinfo.life.hust.edu.cn/)and HGNC database(http://www.genenames.org/),and gene metabolic pathway are searched by KEGG database(http://www.kegg.jp/).Result:2041 diabetic microangiopathy were enrolled in the study.There were 1318 patients with diabetic microangiopathy(There were 734 diabetic retin opathy patients and 138 patient only complicated with diabetic retinopathy;ther e were 468 diabetic nephropathy patients and 96 patient only complicated with diabetic nephropathy;there were 1044 diabetic peripheral neuropathy patients and 379 patient only complicated with diabetic peripheral neuropathy;)723 pati ents without microvascular disease.Univariate logistic regression analysis showe dthat age(OR=1.016,95%CI 1.008-1.023,P=0.000),course of disease,(OR=1.071,95%CI 1.005-1.086,P=0.000),family history(OR=1.306,95%CI 1.085-1.573,P=0.005),hypertension(OR=1.651,95%CI 1.376-1.983,P=0.000),hyperlipi demiadisease(OR=1.270,95%CI 1.056-1.529,P=0.011),cardiovascular disease(OR=1.978,95%CI 1.608-2.433,P=0.000),cerebral vascular disease(OR=1.269,95%CI 1.009-1.595,P=0.042),BMI(OR=1.035,95%CI 1.011-1.059,P=0.003),FBG(OR=1.025,95%CI 1.001-1.050,P=0.045),2hPBG(OR=1.112,95%CI 1.083-1.142,P=0.000),HbA1c(OR=1.100,95%CI 1.053-1150,P=0.000),SBP(OR=1.008,95%CI 1.002-1.013,P=0.004),DBP(OR=0.997,95%CI 0.995-1.000,P=0.024),blood stasis syndrome(OR=1.247,95%CI 1.038-1.502,P=0.018),phle gm and blood stasis syndrome(OR=1.460,95%CI 1.144-1.865,P=0.002),syndr ome of yin deficiency and dryness heat(or=0.444,95%CI 0.326-0.606,p=0.000),syndrome of yang deficiency of spleen and kidney(or=2.335,95%CI 1.549-3.520,p=0.000)are related with diabetic microangiopathy.Multivariate logistic regr ession analysis showed that course of disease(OR=1.052,95%CI 1.036-1.069,P=0.000),family history(OR=1.241,95%CI 1.016-1.517,P=0.035),hypertension(OR=1.315,95%CI 1.052-1.643,P=0.035),cardiovascular disease(OR=1.522,950%CI 1.204-1.924,P=0.000),2hPBG(OR=1.098,95%CI 1.065-1.132,P=0.000),HbAlc(OR=1.043,95%CI 1.002-1.084,P=0.038),blood stasis syndrome(OR=1.251,95%CI 1.025-1.528,P=0.028),phlegm and blood stasis syndrome(OR=1.319,95%CI 1.016-1.712,P=0.038),syndrome of yin deficiency and dryness heat(OR=0.535,95%CI 0.383-0.749,P=0.000)and syndrome of yang deficiency of spleen and kidney(OR=1.660,95%CI 1.074-2.565,P=0.022)are relatedwith d iabetic microangiopathy;course of disease(OR=1.069,95%CI 1.054-1.086,P=0.000),family history(OR=1.324,95%CI 1.085-1.615,P=0.006),2hPBG(OR=1.099,95%CI 1.069-1.129,P=1.129),syndrome of yin deficiencyand dryness heat(OR=0.515,95%CI 0.345-0.768,P=0.001)and syndrome of yang deficiency o f spleen and kidney(OR= 1.536,95%CI 1.072-2.202,P=0.019)are related with DR;age(OR=0.979,95%CI 0.968-0.989,P=0.000),course of disease(OR=1.047,95%CI 1.030-1.064,P=0.000),hypertension(OR=1.697,95%CI 1.311-2.196,P=0.000),cardiovascular disease(OR=1.345,95%CI 1.053-1.718,P=0.018),cere brovascular disease(OR=1.354,95%CI 1.031-1.777,P=0.029 FBG(OR=1.029,95%CI 1.001-1.059,P= 0.044),2hPBG(OR=1.051,95%CI 1.021-1.082,P=0.001),SBP(OR=1.008,95%CI 1.001-1.014,P=0.015),phlegm and blood stasis syn drome(OR=1.438,95%CI 1.099-1.881,P=0.015),syndrome of yin deficiency a nd dryness heat(OR =0.603,95%CI 0.376-0.968,P=0.036),syndrome of yang d eficiency of spleen and kidney(OR=2.286,95%CI 1.583-3.301,P=0.000)are r elated with DN;course of disease(OR=1.043,95%CI 1.029-1.058,P=0.000),f amily history(OR=1.399,95%CI 1.158-1.691,P=0.001),hyperlipidemia(OR=1.328,95%CI 1.049-1.682,P=1.328),cardiovascular disease(OR=1.555,95%CI 1.253-1.929,P=0.000),BMI(OR=1.033,95%CI 1.008-1.058,P =0.009),2hPBG(OR=1.093,95%CI 1.064-1.123,P=0.000),phlegm and blood stasis syndrome(OR=1.386,95%CI 1.088-1.765,P=0.008),syndrome of yin deficiency and dry ness heat(OR=0.683,95%C1 0.487-0.957,P=0.027)and syndrome of yang defici ency of spleen and kidney(OR= 1.541,95%CI 1.060-2.241,P=0.023)are relate d with DPN.Located in the syndromes of the top three are Syndrome of deficiency of Qi and Yin(58.3%),syndrome of blood stasis block(43.4%)and synd rome of phlegm and blood stasis syndrome(18.5%).From the course of stratif ication we can see:course of 5 years or less,52.1%of patients with diabetic microangiopathy;course of 6-10 years,61.8%of patients with diabetic microan giopathy;course of 11-15 years,72.9%of patients with diabetic microangiopat hy;course of 16-20 years,77.6%of patients with diabetic microangiopathy;co urse of more than 20 years,80.9%of patients with diabetic microangiopathy.From HbAlc,HbAlc<7%,49.9%of patients with diabetic microangiopathy,HbAlc in 7-9%,67.6%of patients with diabetic microangiopathy,HbAlc>9%,71.4%of patients with diabetic microangiopathy.From BMI,BMI<18.5kg/m2,53.2%of patients with diabetic microangiopathy,BMI in 18.5-23.9kg/m2,59.7%of patients with diabetic microangiopathy,BMI in 24-27.9kg/m2,66.8%of pat ients with diabetic microangiopathy,BMI≥28kg/m2,69.2%of patients with dia betic microangiopathy.Five risk factors of DR was obtained in the previous st udy,2041 patients with T2DM were matched and 12 pairs eligible(24 patients)were enrolled.The extracted DNA samples were consistent with the experiment al requirements,the results of Hapmap chip scanning data,selected 7691 SNP sites,and finally selected the difference of gene loci,rs9345283,rs738322,rs2844795,rs1727638,rs16984239,rs12505641,rs12142968,rs11243897,rs11175883 in 12 pairs patients.And use the database query to the rs738322 locus in PLA2G6 gene,rs2844795 locus in TRIM31 gene,rsl727638 locus in LINC01626 gene,rs12505641 gene loci at LOC105374524 and rs11243897 loci in AK8 gene;and we can not found gene of rs9345283,rs16984239,rsl2142968 and rs 11175883.Use the KEGG database to find related gene function:PLA2G6 gen e is involved in the regulation of inflammation and lipid metabolism,TRIM31 gene involved in the regulation of immune response,AK8 gene is involved in the negative regulation of epithelial cell migration,we did not find function of LOC105374524 gene and LINC01626 geneConclusion:1 Course of disease,family history,hypertension,cardiovascular disease 2hPBG,HbAlc,BMI,phlegm and blood stasis syndrome,syndrome o f yin deficiency and dryness heatand,syndrome of yang deficiency of spleen a nd kidneyare related with diabetic microangiopathy;course of disease,family h istory,2hPBG,syndrome of yin deficiency and dryness heat and syndrome of yang deficiency of spleen and kidney are related with DR;age,course of dise ase,hypertension,cardiovascular disease,cerebrovascular disease,FBG,2hPBG,SBP,phlegm and blood stasis syndrome,syndrome of yin deficiency and dryne ss heat,syndrome of yang deficiency of spleen and kidney are related with D N;course of disease,family history,hyperlipidemia,cardiovascular disease,BM I,2hPBG,phlegm and blood stasis syndrome,syndrome of yin deficiency and dryness heat and syndrome of yang deficiency of spleen and kidney are related with DPN.2 Considering that PLA2G6 gene may mediate islet secretion and islet cell fun ction through inflammatory mediation,regulate the contractile function of vascu lar smooth muscle,and participate in the occurrence of diabetic retinopathy,Tri m31 gene may be involved in the pathogenesis of diabetic retinopathy by activ ating NLRP3 inflammatory agents;no correlation between ak8 gene polymorphis m and the pathogenesis of DR.