한국의 당뇨병성 신증 및 대혈관 합병증의 발생에서 Angiotensin Converting Enzyme Gene 과 Plasminogen Activator Inhibitor-1 Gene Polymorphism 에 관한 연구

초록

Background: Although development of DM nephropathy in NIDDM patients is associated with poorly controlled blood sugar level and hypertension, the relationship of genetic factors 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 promoter region of the PAI-1 gene are associated with myocardial infarction. The aim of this study was to determine the relationships of these polymorphisms and substance activities to DM nephropathy and macroangiopathy. Methods: 72 NIDDM patients who suffered from DM for more than 6 years and 62 non-diabetic healthy controls were evaluated. After extraction of DNA from peripheral blood, ACE and PAI-1 gene polymorphisms were determined by polymerase chain reaction, SSCP electrophoresis, and silver stain. Serum PAI-1 level was detected by Immulyse PAI-1 ELISA kit (Bipool Sweden). Results: A total of 134 samples were evaluated, and ACE genotypes were DD 27 (20%), ID 88 (66%), and II 19 (14%). PAI-1 genotypes were 4G4G 26 (19%), 4G5G 73 (55%), and 5G5G 35 (26%). The distribution of ACE and PAI-1 polymorphisms according to presence or absence of nephropathy were DD 10, ID 32, II 8, 4G4G 9, 4G5G 31, and 5G5G 10 in the DM nephropathy group, and DD 3, ID 17, II 2, 4G4G 5, 4G5G 12, and 5G5G 5 in the non-nephropathy group. There were no significant differences in the distribution of ACE and PAI-1 genes between the two groups. The distribution of ACE and PAI-1 polymorphisms according to macroangiopathy were DD 6, ID 16, II 3, 4G4G 5, 4G5G 15, and 5G5G 5 in the macroangiopathy group, and DD 7, ID 33, II 7, 4G4G 9, 4G5G 28, and 5G5G 10 in the non-macroangiopathy group. There were no significant differences in the distribution of ACE and PAI-1 genes between macroangiopathy and non-macroangiopathy groups. Serum PAI-1 levels according to PAI-1 gene and ACE gene polymorphisms 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, showing a tendency to be higher in the 4G4G genotype. Conclusion: From the above results, we cannot define the relationships of ACE and PAI-1 gene polymorphisms and PAI-1 activities to DM nephropathy and macrovascular complications of NIDDM patients, but prospective studies including a larger patient population will be required.

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