Molecular Epidemiology Research On Characteristics And Influencing Factors Of Diabetic Nephropathy

The numbers of Type2Diabetes Mellitus(T2DM) rapidly increase in the worldwide. Date to2011, the number of T2DM worldwide was expected to346million and it rised to90million In CHINA. With development of T2DM, Several comorbidities will occurr, including cardiovascular disease, retinopathy, nephropathy, diabetic peripheral nerve diseases, diabetic foot. Diabetic nephropathy is a major microvascular complication of diabetes mellitus, and it can hardly be cured,. It is main death causes of diabetes mellitus. Both environment and genetic factors are responsible for its mechanisms. In recent10years, Diabetic nephropathy has deeply been recearched from cellular and molecular level, and inflammatory molecules and mediators play very important roles in the early stages of diabetic kidney disease. Toll-like recepter2(TLR2) plays key roles in innate and adaptive immune systems, and activates downstream signaling by MyD88and enhances NF-kB, leads to expression and activation of diabetic nephropathy related productions.Objective:To analyse of epidemiological characteristics and risk factors of diabetic nephropathy,and to explore susceptible genotypes on development of complication of T2DM.Then to detect high susceptible people of nephropathy,and provide theoretic data and experiment testimonies for further prevention or controlling development of diabetic nephropathy.Menthods:First, we designed questionnaire, and collected patients from First Affiliated Hospital of Jinan University during1998-2010years. The total number of samples was1015. Questionnaire covered five parts, general information, clinical features, lab testing results and so on. Then we collected52patients’whole blood and selected51control samples matched on age and sex. At last, we extracted DNA with Kit.Results:we divided1015samples into two groups by diabetic nephropathy or not,and maked statistic analysis.The results showed that age(P=0.000), course of the disease (P=0.000) increased in patient group compared with control group. There were significant differences among family history(P=0.005), education level((P=0.001), and payment (P=0.000).In clinical features we found polydipsia、diuresis (P=0.000),mouth dry((P=0.000),fatigue (P=0.000), limbs numb (P=0.000), eyesight obscure (P=0.000), legs edema (0.000), weight lowing (P=0.000), limbs and trunk pain (P=0.000), hyperorexia and rapid hungering (P=0.004), wound not cured for a long time (P=0.006), are worse in patients than in control group. Glycosylated hemoglobin (P=0.005),fastingblood-glucose (P=0.011), microalbuminuria (P=0.000), serum total cholesterol (P=0.005), glycerol triester (P=0.013), serum creatinine (P=0.000), blood uric acid (P=0.000), were worse than control group. However, postprandial2h c-peptide(P=0.034) was lower in patients than control group.By logistic regression analysis, the results showed that age(OR95%CI:1.17,1.018-1.060, P=0.000), course of the disease (OR95%CI:1.16,1.099-1.214,P=0.000), family history OR95%CI:1.68,1.170-2.413,P=0.005were risk factors of diabetic nephro-pathy. Some clinical symptoms such as polydipsia、diuresis, fatigue, limbs numb, eyesight obscure, legs edema, palpitation, astasia, limbs and trunk pain, wound not cured for a long time,were important features of development of diabetic nephropathy. Legsedema(OR95%CI:6.60,3.767-11.554,P=0.000),astasia (OR95%CI:17.20,1.900-155.627,P=0.011) limb sand trunk pain (OR95%CI:5.49,2.759-10.925,P=0.000),skin wound not cured for a long time (OR95%CI:3.61,1.090-11.635,P=0.036),glyceroltriester (OR95%CI:1.11,1.026-1.205,P=0.010) serum creatinine (OR95%CI:1.02,1.006-1.031,P=0.003) were risk factors of diabetic nephropathy. We screened five single nucleotide polymorphisms (SNPs) of TLR2gene, including rs1898830(Arg677Trp), rs469480(T-16934A),rs7656411(3’UTR),rs3804100(Ser450Ser) and rs3804099(Asn199Asn). TLR2rs3804100(T/C) and rs3804099(T/C), these genes’TC+CC genotypes may be the protection factors with complications of type2diabetes mellitus.Conclusions:Age and course of the disease were risk factors of development of diabetic nephropathy that can not be controlled. Education level, diabetes mellitus family history, polydipsia、diuresis, fatigue, limbs numb, eyesight obscure, legs edema, palpitation, astasia, limbs and trunk pain, skin wound not cured for a long time, glycerol trimester, serum creatinine are risk factors of diabetic nephropathy. Rs3804100and rs3804099in TLR2gene may be susceptible for complications of type2diabetes mellitus.