PECAM-1 gene polymorphism (rs668) and subclinical markers of carotid atherosclerosis in patients with type 2 diabetes mellitus.

The platelet endothelial cell adhesion molecule 1 (PECAM-1) plays an important role in many inflammatory processes, including the development of atherosclerosis. Polymorphism rs668 of the PECAM-1 gene (373C/G) is functional, and it was reported to be associated with increased serum levels of PECAM-1. We investigated the association between the rs668 polymorphism of PECAM-1 and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Geno-typing of the PECAM-1 gene polymorphism (rs668) was performed using KASPar assays. The control examinations were performed 3.8 ± 0.5 years after the initial examination. Higher CIMT was found in patients with T2DM in comparison with subjects without T2DM. Statistically sig-nificantly faster progression of the atherosclerotic markers was shown in subjects with T2DM in comparison with the control group. When adjusted to other risk factors, the rs668 GG genotype was associated with an increased risk of carotid plaques in subjects with T2DM. We concluded that our study demonstrated a minor effect of the rs668 PECAM-1 on markers of carotid atherosclerosis in subjects with T2DM.

Association of the ACE rs4646994 and rs4341 polymorphisms with the progression of carotid atherosclerosis in slovenian patients with type 2 diabetes mellitus.

The current study was designed to reveal possible associations between the angiotensin-converting-enzyme (ACE) gene polymorphisms (rs4646994 and rs4341) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM) in a 4-year-long follow-up study. Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. Genotyping of ACE polymorphisms was performed using KASPar assays, and ultrasound examinations were performed twice (at the enrollment and at follow-up). With regard to the progression of atherosclerosis in subjects with T2DM, statistically significant differences were demonstrated in the change of the sum of carotid plaques thickness for the rs4646994 polymorphism. We did not demonstrate an association between the tested polymorphisms (rs4646994 and rs4341) and either carotid intima media thickness (CIMT) or CIMT progression in a 3.8-year period. In our study, we demonstrated that subjects with T2DM with the DD genotype of the rs4646994 [ACE insertion/deletion (I/D)] polymorphism had faster progression of atherosclerosis in comparison to subjects with other genotypes.

Polymorphisms +45T>G and +276G>T of the adiponectin gene does not affect plasma adiponectin level and carotid intima-media thickness in patients with diabetes mellitus type 2.

AIM: Despite increasing evidence of adiponectin's anti-inflammatory and antiatherogenic effects, its role in atherogenesis remains uncertain. The aim of the present study is to investigate the association between +45T>G and +276G>T polymorphisms of the adiponectin gene and both plasma adiponectin levels and carotid intima-media thickness in patients with diabetes mellitus type 2. METHODS: 301 diabetic patients, divided into three categories on the basis on BMI were enrolled in the study. Carotid intima-media thickness (CIMT) was assessed ultrasonographically. Plasma adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Genotypes were determined by real-time PCR. RESULTS: Adiponectin level and prevalence of the G allele of 45T>G polymorphism decreased significantly with increasing BMI category. G allele of +45T>G polymorphism was associated with higher plasma adiponectin level only after adjustment for age, sex and BMI. No statistically significant difference in CIMT and +276T>G genotypes distribution was observed between BMI categories. None of the polymorphisms as well as plasma adiponectin level was associated with CIMT after adjustment for covariates. CONCLUSION: The G allele of the +45T>G polymorphism is not independently associated with plasma adiponectin level and is not associated with CIMT. +276G>T polymorphism is not associated with plasma adiponectin levels and CIMT in diabetic patients.

Association of manganese superoxide dismutase and glutathione S-transferases genotypes with carotid atherosclerosis in patients with diabetes mellitus type 2.

AIM: The aim of the present study was to test the association between genetic polymorphisms with functional effects on redox regulation: Ala16Val of manganese superoxide dismutase (MnSOD or SOD2), polymorphic deletions of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1 and carotid atherosclerosis in patients with type 2 diabetes. METHODS: The study enrolled 287 subjects with type 2 diabetes. Carotid atherosclerosis was quantified by ultrasonography as carotid intima-media thickness (CITM), plaque score from 0 to 6 and plaque type from 1 to 5. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The highest triglyceride level was observed in patients with MnSOD Val/Val genotype. Other polymorphisms did not show significant association with clinical parameters. We did not observe significant differences in MnSOD, GSTM1 and GSTP1 genotypes distribution according to CIMT, plaque type or plaque score. After adjustment for age, sex, smoking, BMI, lipid parameters and duration of hypertension and diabetes carriers of GSTT1-0 genotype showed an increased risk for higher plaque score (OR=2.29; p=0.012), but no association with CIMT and plaque stability was observed. Carrying of both GSTM1-0 and GSTT1-0 did not influence clinical parameters but increased risk for higher plaque score (OR=2.59; P=0.018). CONCLUSION: We did not find a significant association between the MnSOD, GSTM1 and GSTP1 polymorphisms and carotid atherosclerosis. The GSTT1-0 genotype and GSTT1-0/GSTM1-0 haplotype might be a potential determinants of susceptibility to advanced atherosclerosis in patients with type 2 diabetes mellitus.