| Objective and backgroundDiabetic nephropathy (DN) is now the leading cause of end-stage renal failure. Epidemiological studies have shown that the prevalence of DN varies widely among different diabetic populations. It is well known that some diabetic patients develop severe complications early despite careful control of their blood glucose levels, while others have no complications after many years of diabetes. Suggesting that the genetic factor is involved in the pathogenesis of DN. Aldose reductase (AR), the rate-limiting enzyme in the polyol pathway , is a potential candidate gene product. It has been reported that AR gene expression is increased in PBMC of type 1 diabetic patients with nephropathy compared to those without nephropathy. Transgenic mice expressing high levels of AR are susceptible to diabetic microangiopathy. So the high expression of AR in tissues maybe the important risk for diabetic microangiopathy. The present study is to investigate the AR mRNA level in PBMC of type 2 diabetic patients and to evaluate the relationship between the levels of AR mRNA level and the risk of diabetic nephropathy.MethodsA total of 54 type 2 diabetic patients and 35 normal controls (group l.Gj) were studied. All type 2 diabetics were divided into 3 groups according to Mogesen's principal: group 2 (62): patients with normal albuminuria, urinary albumin excretion (UAE)<30mg24/h; group 3 (G3): incipient DN , 30mg/24h^ UAE<300mg/24h; group 4 (G4): clinical DN, UAE5?300mg/24h. AR mRNAlevel in PBMC was analyzed quantitatively by RT-PCR method. The results were expressed as mean ?standard deviation. T-test and one-way analysis of variance of biological data were performed. Multiple comparison was accomplished by Student-Newman-Keuls method. All statistic tasks were accomplished with the software of SPSS 6.0.Results1. AR mRNA level in PBMC of type 2 diabetic patients was significantly higher than that in PBMC of normal controls (0.74+0.66 vs 0.29 ?.10, P=0.009). There were no significant difference in age, blood pressure, SCr between the two groups. The level of FPG was significantly higher in type 2 diabetic patients than that in normal controls(9.47?.31 mmol/L vs 4.72 + 0.58 mmol/L, PO.05).2. Among diabetics, the AR mRNA levels of each groups were: G2:0.54?0.39; G3: 0.73 ?.39; G4:1.47?.02. The SCr was significantly higher in G4 than that in GI> G2 and G3 (P<0.05). The AR mRNA level in G4 was significantly higher than that in 62 and G3 (PO.05). And the AR mRNA level in G3 was significantly higher than that in 62 (PO.05). No significant difference was found in age, blood pressure, hemoglobin Aic or duration of diabetes among three groups.3. Correlation analysis: There have positive correlation between SCr and AR mRNA levels in diabetic patients (r=0.3569, P=0.006). No correlation was found in FPGx HBAlc^ TC, TG> DBP> SBP^ duration with AR mRNA level.Conclusions1 .Type 2 diabetic patients have a significantly higher expression of AR mRNA in PBMC than normal controls.2.Type 2 diabetic patients with clinical DN have a significantly higher expression of AR mRNA than that with incipient DN and that without albuminuria.3.There have positive correlation between SCr and AR mRNA, r=0.3569, P=0.006.4.RT-PCR is an ideal method to analyze AR mRNA level quantitatively.
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