Korean J Nephrol.  2001 Jul;20(4):565-575.

Polymorphisms of Angiotensin Converting Enzyme and Plasminogen Activator Inhibitor-1 Genes in Diabetic Nephropathy and Macroangiopathy in NIDDM Patients

• Yoon JW
• Jo SK
• Han SY
• Cha DR
• Cho WY
• Kim HK

Abstract

BACKGROUND: Although development of DM nephropathy in NIDDM patients is associated with poorly controlled blood sugar level and hypertension, relationship of genetic factor is also emphasized. Recent studies showed that an insertion or deletion (I/D) polymorphism in the ACE gene and a 4/5- guanine tract polymorphism in the promotor region of the PAI-1 gene are associated with the myocardial infarction. The aim of this study were to determine the relationships of these polymorphism and substance activities to DM nephropathy and macroangiopathy.
METHODS
72 NIDDM patients who suffered from DM more than 6 years and 62 non-diabetic healthy control were evaluated. After extraction of DNA from peripheral blood, ACE and PAI-1 gene polymorphisms were determined by polymerase chain reac tion, SSCP electrophoresis and silver stain. Serum PAI-1 level was dctected by Immulyse PAI-1 ELISA kit(Bipool Sweden).
RESULTS
Total 134 samples were evaluated and ACE genotype were DD 27(20%), ID 88(66%), and II 19(14%). PAI-1 genotype were 4G4G 26(19%), 4G5G 73(55%), and 5G5G 35(26%). The distribution of ACE and PAI-1 polymorphism according to presence or absence of nephropathy were DD 10, ID 32, II 8, 4G4G 9, 4G5G 31, and 5G5G 10 in DM nephropathy group and DD 3, ID 17, II 2, 4G4G 5, 4G5G 12, and 5G5G 5 in non-nephropathy group. There were no significant differences in the distribution of ACE and PAI-1 gene between the two groups. The distribution of ACE and PAI-1 polymorphism according to macroangiopathy were DD 6, ID 16, II 3, 4G4G 5, 4G5G 15, and 5G5G 5 in macroangiopathy group and DD 7, ID 33, II 7, 4G4G 9, 4G5G 28, and 5G5G 10 in non-macroangiopathy group. There were no significant differences in the distribution of ACE and PAI- 1 gene between macroangiopathy and non-macroangiopathy groups. Serum PAI-1 level according to PAI-1 gene and ACE gene polymorphism were 4G4G 47.99+/-19.73, 4G5G 40.19+/-18.49, 5G5G 40.37+/-20.99 ng/mL, DD 37.99+/-16.64, ID 44.80+/-20.35, and II 31.92+/-12.98 and had a tendency that is higher in 4G4G genotype.
CONCLUSION
From the above results, we cannot define the relationships of ACE and PAI-1 gene polymorphism and PAI-1 activities to DM nephropathy and macrovascular complications of NIDDM patients, but prospective studies including more patients population will be required.

Keyword

Angiotensin II; Angiotensin converting enzyme gene polymorphism; Plasminogen activator inhibitor-1 gene polymorphism

MeSH Terms

Angiotensin II
Angiotensins*
Blood Glucose
Diabetes Mellitus, Type 2*
Diabetic Nephropathies*
DNA
Electrophoresis
Enzyme-Linked Immunosorbent Assay
Fibrinogen
Genotype
Guanine
Humans
Hypertension
Myocardial Infarction
Peptidyl-Dipeptidase A*
Plasminogen Activator Inhibitor 1
Plasminogen Activators*
Plasminogen*
Polymorphism, Single-Stranded Conformational
Promoter Regions, Genetic
Silver
Angiotensin II
Angiotensins
Blood Glucose
DNA
Fibrinogen
Guanine
Peptidyl-Dipeptidase A
Plasminogen
Plasminogen Activator Inhibitor 1
Plasminogen Activators
Silver