The Relationship Between ACE And Its Homolog Gene Polymorphism And Type 2 Diabetic Nephropathy

Objective:To investigate whether angiotensin converting enzyme gene insertion/deletion polymorphism and ACE2 gene single nucleotide polymorphism attributes to the susceptibility and progression to type 2diabetic nephropathy.Methods:144 hospitalized patients with type 2 diabetes mellitus were selected in Nephrology and Endocrinology department from October 2005 to June 2006. All the patients without hypertension had not used ACEI or ARB in the past 6 months. Patients with type 2 diabetes mellitus were divided into two groups defined by the urinary albumin excretion of 24 hour, which consisted of non-diabetic nephropathy group and diabetic nephropathy group. General clinical information ,such as body height,weight, blood pressure, fasting blood glucose, glycosylated hemoglobin, cholesterol, triglyceride. blood urea nitrogen, serum creatinine, body mass index and creatinine clearance rate were measured. Patients with DN were divided into two groups defined by serum creatinine clearance rate, which consisted of DN-1 group (Ccr≥60ml/min) and DN-2 group (Ccr<60ml/min). 67 normal subjects as control were from the health examination center of our hospital. The gene polymorphisms of ACE and ACE2 were examined by polymerase chain reaction-restriction fragment length polymorphismanalysis. All data were analysised by SPSS13.0.Results:1. The PCR products of ACE polymorphism include three types of 394bp (II), 106bp (DD), 394bp+106bp (ID); The PCR-RFLP products of ACE2 polymorphism include three types of 220bp + 917bp (G), 220bp+271bp+644bp (A), 220bp+271bp+644bp+917bp (AG).2. The difference of blood pressure and creatinine clearance rate between DN group and non-diabetic nephropathy group has statistically significance (P<0.05).The difference of systolic blood pressure and creatinine clearance rate in male patients between DN group and non-diabetic nephropathy group has statistically significance (P<0.05); The difference of blood pressure and creatinine clearance rate in female patients between DN group and non-diabetic nephropathy group also has statistically significance (P<().05).There was no difference of general clinical information among the three genetypes of ACE (P>0.05).3. There was no difference of genotype and allele frequency of I/D polymorphism in ACE gene between control subjects and type2 diabetes, DN (P>0.05).The DD genotype frequency in DN group was significantly higher than that of non-DN group (P<0.05).The DD genotype and D allele frequency in DN-2 group were significantly higher than that of DN-1 group (P<0.05).4. There was no difference of gene distribution of ACE2 between control subjects and type2 diabetes, DN.The A gene frequency in male DN group was significantly higher than that of non-DN group (P<0.05); in female DN group, the A gene frequency was higher than that of non-DN group, but there was no statistical significance (P>0.05). Conclusions:1. Polymorphism of insertion/deletion in ACE gene may contribute to susceptibility and progression of DN.2. The G8790A polymorphism of ACE2 may be contribute to genetic susceptibility to DN, especially in male patients.