The aim of the present study was to investigate the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the ultrasonographically evaluated severity and characteristics of carotid artery atherosclerosis in subjects with diabetes mellitus type 2.
We assessed 184 subjects with diabetes mellitus type 2, 75 males and 109 females, mean age 61.4+/-7.7 years. All subjects were receiving oral antidiabetic drugs for glycemic control and were free of cardiovascular events. The ACE genotype was analyzed by the polymerase chain reaction (PCR) technique. The ultrasonographic examination of the carotid arteries was performed in both B-mode imaging and Doppler ultrasound. The common carotid artery intima-media thickness was assessed 15-20 mm proximal to the dilatation of the carotid bulb. The atheromatous lesions were classified according to their echogenic characteristics as predominantly echolucent, mixed and predominantly echogenic with under 30, 30-70 and over 70% of the total plaque area echogenicity, respectively.
From the total cohort 29 (15.8%) subjects had the II, 86 (46.7%) the ID and 69 (37.5%) the DD ACE genotypes. The mean carotid artery diameter stenosis was 37+/-17%, 43+/-19% and 40+/-20% (p=NS) and the intima media thickness was 0.94+/-0.24 mm, 0.97+/-0.20 mm and 0.98+/-0.20 mm (p=NS) in the II, ID and DD subgroups, respectively. When the echogenicity was analyzed according to the ACE I/D polymorphism, 12 subjects (41.4%), 13 (44.8%) and 4 (13.8%) with II genotype had predominantly echogenic, mixed and predominantly echolucent lesions, respectively. The ID genotype diabetics were found to have predominantly echogenic plaques in 41 cases (47.7%), mixed in 30 (34.9%) and predominantly echolucent in 15 cases (17.4%). From the 69 DD subjects 19 (27.5%) had predominantly echogenic plaques, 26 (37.7%) had mixed and 24 (34.8%) had predominantly echolucent lesions. Predominantly echolucent plaques were more frequently encountered among diabetics with the DD genotype (p<0.05), even after correction for demographic characteristics, the main risk factors of atherosclerosis and blood glucose control.
The ACE genotype seems to be associated with the echogenicity of carotid artery atheromatosis but not with the common carotid artery intima media thickness or the degree of internal carotid artery stenosis in subjects with type 2 diabetes mellitus. The DD genotype may be implicated in the increased cardiovascular risk that characterizes echolucent plaques.
"Several studies have shown that the DD genotype is associated with a higher risk for myocardial infarction (MI) and CAD (Naftilan et al., 1989; Campbell-Boswell et al., 1981). Some studies showed a relation of atherosclerosis with presence of the D allele, (Castellano et al., 1995; Nergizoglu et al., 1999; Pujia et al., 1996; Hosoi et al., 1996) while others have failed to show such association (Diamantopoulos et al., 2002; Dessi-Fulgheri et al., 1995). The majority of the studies conducted until now were based on relatively small sample sizes, which may in part explain the inconsistency, particularly when interactions were studied (Lohmueller et al., 2003) . "
[Show abstract][Hide abstract] ABSTRACT: Genetic factors are important in the pathogenesis of coronary artery disease (CAD). The I/D polymorphism in the Angiotensin converting enzyme (ACE) gene is a genetic risk factor for CAD patients who have a history of Myocardial Infraction (MI). We investigated the association between I/D polymorphism of the ACE gene and the presence of CAD in one hundred patients (79 males and 21 females, aged between 21-82) who underwent diagnostic coronary angiography and compared with one hundred patients-as controls (62 males and 38 females, aged between 20-72) who had false symptoms of CAD. The presence of risk factors including age, hypertension, hypercholesterolemia, tobacco use, diabetes mellitus and hyperuricemia was also determined. ACE I/D polymorphism was detected by polymerase chain reaction. The D allele frequency was higher (p <0-01) in CAD patients. The logistic regression analysis indicated that the D allele in association with classical risk factors had the potential to induce CAD, with odds ratio = 0.58(95% CI; 0.37-0.90). This study revealed that, the I/D polymorphism of ACE gene (carrying D allele) was found to be an independent risk factor for CAD in the studied South Indian population. The number of risk factors did not alter the frequency of ACE gene genotype among patients with CAD, however, in normotensives, the odds ratio of DD-genotype was significantly higher, as the D allele of ACE gene polymorphism was found to be associated with morbidity in CAD in this study population.
"We preserved these cases as it not only minimised bias, but also pointed towards a very important and novel concept of the genetic predisposition to higher CCIMTs irrespective of risk factors. Such studies proposing the importance of genetic factors have been reported by Lange et al. , Diamontopoulos et al.  and also, very recently by Moskau et al. . Apart from age, proteinuria also had a correlation with increased CCIMT in this study. "
[Show abstract][Hide abstract] ABSTRACT: Background and objectives: The evaluation of the Common Carotid Intima Media Thickness (CCIMT) assumes a special role in patients with diabetes mellitus because of being an indicator of the pan effect of atherosclerotic risk factors and an important predictor of catastrophic vascular events. Therefore, the present study was undertaken with the objective of correlating CCIMT with the numerous risk factors of atherosclerosis in diabetes patients. Subjects and methods: In the present study, 90 type 2 diabetic patients [67 males and 23 females, having assessed the CCIMT] with an age range from 32 to 78 years, with and without atherosclerotic events were recruited. Measurement of common carotid intima media thickness was measured on B-mode ultrasonography using high frequency linear transducer on a "GE LogiQ 700". Results: The results showed that significant positive correlation and independent association of CCIMT turned out with the variables age and proteinuria. However, waist/hip ratio, duration of diabetes mellitus, systolic blood pressure, glycosylated hemoglobin, triglyceride, and total cholesterol/HDL cholesterol also had positive correlation with CCIMT, but they could not achieve the level of statistical significance. The patients who had higher CCIMT values and high odds ratios for atherosclerotic events had significantly higher durations of diabetes, hypertension and presence of dyslipidemia. Conclusion: This study has proven that age and proteinuria are the strongest correlates of CCIMT in type 2 diabetes mellitus. It is also suggested that further large size studies are needed to reconfirm similar results.
International Journal of Diabetes Mellitus 04/2009; 1(1):7-10. DOI:10.1016/j.ijdm.2009.03.002
[Show abstract][Hide abstract] ABSTRACT: Increased carotid artery intima-media thickness is associated with an increased risk of coronary heart disease or cerebrovascular disease and is a powerful predictor of cardiovascular and cerebrovascular outcomes. Consequently, the measurement is now used in a number of case control, cohort and familial and linkage studies as an intermediate phenotype for the investigation of the genetic and environmental determinants of atherosclerosis. The aim of this paper is to review the most recent available data on the genetic determinants of carotid intima-media thickness.
Genes could account for a significant amount of variation in carotid intima-media thickness: up to 30-66%. Carotid intima-media thickness progressed more rapidly with age in familial hypercholesterolemia patients than in patients without his condition. Familial hypercholesterolemia patients with a null LDL receptor allele tended to have higher carotid intima-media thickness than patients carrying the LDL receptor defective allele. Small association studies showing positive or negative results with the angiotensinogen gene variants as well as with the angiotensin converting enzyme I/D polymorphism add to the confusion in this largely controversial area. Differing results may depend on the vascular territory and genetic background. New associations have been described in small studies.
Studies on the association of polymorphisms and intima-media thickness are frequently disappointing and lead occasionally to conflicting results. Among study limitations is the fact that mostly single gene effects are considered; longitudinal cohort studies may be more appropriate than case control studies. Ongoing large prospective population studies and clinical trials have integrated the measurements of intima-media thickness and genotype determination with a genomic approach. As a result, in the near future we may see more important and robust results with significant consequences on our understanding of genetic determinants of atherosclerotic cardiovascular disease.
Current Opinion in Lipidology 05/2003; 14(2):191-200. DOI:10.1097/01.mol.0000064050.08840.2b · 5.66 Impact Factor
Luckni Sellahewa, Corniche Khan, Sindujah Lakkunarajah, Iskandar Idris
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