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The predicting effects of ACE gene and PAI-I gene polymorphisms on CCA-IMT progression in newly diagnosed T2DM

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Author:
No author available
Journal Title:
JOURNAL OF CHINESE PHYSICIAN
Issue:
7
DOI:
10.3760/cma.j.issn.1008-1372.2009.07.002
Key Word:
肽基二肽酶A/遗传学;纤溶酶原激活物抑制物1/遗传学;多态现象,遗传;糖尿病,2型/病理学;血管中膜;Peptidyl-dipeptidase A/GE;Plasminogen activator inhibitor 1/GE;Polymorphism,genetic;Diabetes mellitas,type 2/PA;Tunica media

Abstract: Objective The study was to investigate the relationship among angiotensin 1-converting enzyme(ACE), plasminogen activator inhibitor-1 (PAI-1)gene polymorphisms and the common carotid artery (CCA-IMT), and the predicting effects of them on CCA-IMT in newly diagnosed type 2 diabetes (T2DM). Methods The polymorphisms of ACE (I/D) gene and PAI-I (4G/5G) gene were deter-mined by polymemse chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific polymerase chain reaction (AS-PCR) method in 308 cases with T2DM. CCA-IMT was compared among the groups with different genotypes of ACE and PAI-1. The in-dependent or synergistic effects of the ACE I/D and PAI-1 40/5G polymorphisms on CCA-IMT in 308 patients with T2DM were analyzed with multivariate linear regression. Then the 156 newly diagnosed type 2 diabetics (durations< I year) without AS received the maltifactorial targeted intervention, including taking aspirin and controlling blood glucose, blood pressure, blood lipid and body weight. The differences of metabolic control, ACE (I/D) and PAId (40/5G) gene polymorphisms were analyzed. Logistic regression analysis was used to analyze the eorrelation among the CCA-IMT, ACE (I/D) and PAI-1 (4G/5G) polymorphisms. Results Patients with ACE DD genotypes had higher CCA-IMT than those with ACE-Ⅱ or ACE ID genotypes. Patients with both ACE DD and PAI-1 404G genotypes had a higher CCA-IMT than those with any other pairs of genotypes. Multivariate linear regression analysis showed that ACE DD and PAI-1 4G4G gene polymorphisms had synergistic effect on the CCA-IMT in T2DM patients. After 2 years multifactorial intervention, the frequencies of PAI-1 4G alleles and 404G genotypas were lower than those in the CCA-IMT non-inereasing group. Conclusions These findings indicate that the ACE-DD geno-type and its synergistic effects with the PAI-1 4G/4G genotype are independent risk factors for the CCA-IMT in T2DM patients. Under multi-factorial intervention for 2 years, PAI-1 4G/4G genotype may be a negative predictor for the progression of CCA-IMT in T2DM patients.

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