Relationship Between Angiotensin Ⅰ Converting Enzyme Gene And Plasminogen Activator Inhibitor 1 Gene Polymorphism And Type 2 Diabetes Nephropathy

[Objective] To investigate the frequency and functional significance of angiotensin I converting enzyme(ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and their relationship to type 2 diabetes with nephropathy.[Methods) The allele frequency and the genotype distribution of the polymorphism of ACE gene and PAI-lgene in the group of 58 normal subjects and 217 type 2 diabetes were detected by means of polymerase chain reaction (PCR). According to measurement of the albumin-to-creatinine ratio(ACR) in overnight collection of the urine(8pm~8am), the group of type 2 diabetes was devided to diabetic nephropathy positive(DN+) group and diabetic nephropathy negative(DN-) group. PAI-1 antigen was quantified by a ELISA assay. Weight, height, arterial blood pressure, total cholesterol, triglycerids, HbA1C were measured. Insulin was determined with radio -immunoassay kit. Body mass index, insulin sensitivity were calculated.[Results]1,2 alleles (I and D)and 3 genotypes(II, ID and DD)were detected in ACE gene. 2 alleles (4G and 5G)and 3 genotypes(5G/5G, 4G/5G and 4G/4G)were detected in PAI-1 gene. 2, The genotype distribution of the ACE gene polymorphism were different among normal subjects , patients with and without diabetic nephropathy (x2=57. 459 p < 0. 05), A higher prevalence of ACE D allele served among patients with diabetic nephropathy than those without(0. 576vsO.250, x2=43.573, p<0.05). the genotype distribution of the gene polymorphism were different among normal subjects, patients with and without diabetic nephropathy (x2=49. 341 p < 0. 05), A higher prevalence of PAI-1 4G allele served among patients with diabetic nephropathy than those without (0.576 vsO. 300, x2=31.480, p<0. 05). 3, A higher prevalence of diabetic retinopathy among patients with PAI-1 4G/4G genotype than those with PAI-14G/5G and 5G /5G genotypes( p< 0. 05). The patients with ACE D allele had more PAI-1 antigen than those with ACE II genotype (P<0.05) . The patients with PAI-1 4G allele had more PAI-1 antigen than those with PAI-1 5G/5G genotypes (P < 0. 05) . 4, The association of PAI-1 antigen and serum triglycerids was effected by the PAI-1 genotypes, The PAI-1 antigenserum triglycerids was effected by the PAI-1 genotypes, The PAI-1 antigen in the patients with PAI-1 4G/4G genotype was related to serum triglycerids (r=0. 43, p< 0. 05) . 5, Multiple logistic regression analysis of the risk factors associated with diabetic nephropathy revealed that the DD genotype of ACE gene and 4G/4G genotype of PAI-1 gene act as the independent risk factors for diabetic nephropathy.6, Coexistence of ACE D allele and PAI-14G/4G was associated with increased risk of type 2 diabetic nephropathy.[Conclusion] 1, A higher prevalence of ACE DD genotype or D allele served among patients with diabetic nephropathy than those without. A higher prevalence of PAI-1 4G/4G genotype or 4G allele served among patients with diabetic nephropathy than those without. The DD genotype of ACE gene and 4G/4G genotype of PAI-1 gene acted as the independent risk factors for diabetic nephropathy. 2, The patients with ACE D allele had more PAI-1 antigen than those with I allele. The patients with PAI-1 4G allele had more PAI-1 antigen than those with 5G allele. In this report, we have demonstrated that the ACE and PAI-1 genotype could effect PAI-1 gene expression. 3, The presence of combinations of ACE D allele and PAI-1 4G/4G may involved in the generation of diabetic nephropathy.