Relationships Between Paraoxonase Family And Diabetic Vascular Complications In Type 2 Diabetes Mellitus

Type 2 diabetes mellitus(T2DM) is seriously endangering human health because of its high mortality and disablity rate. T2DM can induce many long-time complications, including microvascular and macrovascular complications.More and more evidence in both experimental and clinical studies suggested that oxidative stress and lipid peroxidation play an important role in the pathogenesis of diabetic vascular complications. Hyperglycemia engenders free radical, it also impairs the endogenous antioxidanl defense system, Increased product ion of free radicals and impaired antioxidant dei'enses exist in diabetes mellitus at the same time. Diabetes is usually accompanied by lipid disorder. Gly-LDL and small ,dense LDL are increase. Under oxidiative stress, these types of LDL are susceptible to oxidization. Increased oxidative stress and lipid peroxidation can promote the development of diabetic vascular complications. In recent years, some foreign studies found serum paraoxonase-1 (PON1), an enzyme located in high -density lipoprotein (HDL), possesses many biological activities. 1. Prevent lipid peroxidation of LDL and HDL. 2. Destroy the biological activity of oxidized phospholipid in ox-LDL. 3. Hydrolyze lipid peroxidesin human atherosclerotic lesions. 4. Hydrolyze platelet-activating factor. 5. Hydrolyze hydrogen peroxide. In brief, PON1 can reduce high oxidative stress and 1 ipid peroxidation through many strategies. Many cl inical studies indicated that PON1 is reduced in several groups, such as individuals with familial hyporcholpsternlapmia, rornnnry artery disense (CAD) nnd type 2 diabetes mellitus. PON2 is another member of paraoxonase gene family .Experiments in vitro suggested that PON2 protein has antioxidant activity similar to PON1. Some clinical studies shown that the PON2 S allele at codon 311 is a risk factor of coronary artery disease. But a few studies could not find the association. Some scholar found the PON2 311 gene polymorphism related to serum POM activity.The aim of this study is to probe the correlation between PON family and diabetic vascular complications. Materials and methodsWe designed a case-control study. The subjects of the study consisted of following groups: (l)Diabetes Mellitus(DM) group (47 patients); (2) Coronary Heart Disease (CHD) group (45 patients); (3) DM complicated by CHD group (43 patients); (4) DM complicated by CI group (23 patients); (5) DM complicated by DN group (38 patients); (6) DM complicated by DN and DR (30 patients); (7) normal-control group (40 patients). PON2 gene 311 S/C polymorphism was evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), and serum PON1 activity was determined by measuring the hydrolysis of phenylacetate at 270nm. MDA concentration was determined by photometer. Results1. PON1 activity of DM patients and DM with vascular complications patients was significantly lower than that of control subjects. Further more, PON1 activity of DM with CHD, CI, DN and DR patients was lower than that of DM patients.MDA concentration of DM patients and DM with vascular complications patients was significantly higher than that of control subjects. MDA concentration of DM with CHD, CI, DN and DR patients was further higher than DM patients.2. The frequency of the Paraoxonnso-2 SS genotype and S allole in DM with CHD or DN patients were significantly higher than that of control subjects , DM patients and CHD patients (P<0. 05). There was no difference in genotype frequencies or allele frequencies among control subjects, DM patients and CHD patients (P>0. 05).3. PON1 activity was negative correlated with MDA concentration. PON1 activity was associated with PON2 311 genotype. Serum PON1 activity decreased in the order of CC > SC > SS.4. Logistic regression analysis results suggested that BMI , PON1 activity and PON2 genotype were risk factors of T2DM complicated by CHD and DN. Further more, BMI and PON1 activity were independent risk factors of T2DM complicated by CHD and DN.Conclusions1. Maybe decreased ser...