Matrix metalloproteinase-3 gene polymorphism (rs3025058) affects markers atherosclerosis in type 2 diabetes mellitus.

BACKGROUND: The study was designed to test the possible association between either polymorphisms of the matrix metalloproteinase-9 (MMP-9) gene (rs17576, rs3918242) or the MMP-3 5A/6A gene polymorphism (rs3025058) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The second aim of the study was to demonstrate an association between either the rs17576, rs3918242 or rs3025058 and subclinical markers of coronary artery disease in the same subset of patients with T2DM. PATIENTS AND METHODS: A total of 595 subjects with T2DM and 200 subjects without T2DM (control group) were enrolled in the prospective study. Subclinical markers of carotid atherosclerosis were assessed ultrasonographically. Additionally, in a subset of subjects with T2DM a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of all three polymorphisms (rs17576, rs3918242, rs3025058) was performed with real-time PCR systems. RESULTS: The comparison of atherosclerosis parameters was performed with regard to different genotypes of MMP-9 rs17576, rs3918242, and MMP-3 rs3025058 polymorphisms upon enrolment and during follow-up. In our study, we found an association between the MMP-3 rs3025058 and CIMT at the time of recruitment. Multiple linear regression analysis revealed the association of either the A- allele or the A- genotypes of the rs3025058 (MMP-3) with carotid intima media thickness (CIMT) progression in a 3.8-year follow-up. We demonstrated the effect of the rs3025058 on subclinical markers of coronary atherosclerosis (coronary calcium score, number of coronary arteries with more than 50 % stenosis, and presence of at least one vessel with more than 50 % stenosis). CONCLUSIONS: We found an association between the MMP-3 rs3025058 and subclinical markers of carotid (CIMT) and coronary atherosclerosis at the time of recruitment. Moreover, we demonstrated the effect of the MMP-3 rs3025058 on CIMT progression in the 3.8-year follow-up in patients with T2DM.

Polymorphism rs5498 of the ICAM-1 gene affects the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus.

BACKGROUND: Adhesion molecules are involved in the development of atherosclerosis. An increased level of the ICAM 1 molecule is associated with numerous inflammatory diseases including atherosclerosis of carotid arteries. The rs5498 (K469E) polymorphism of the ICAM-1 gene leads to an increase in the level of serum ICAM. We investigated the association between the rs5498 (K469E) polymorphism of the ICAM-1 gene and the progression of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). METHODS: The study included 595 patients with T2DM and 200 subjects in the control group without T2DM. The control examination was made 3.8 years after the initial examination. Indicators of atherosclerosis (carotid intima-media thickness (CIMT), total plaque sum and sum of the plaques thickness) were detected by ultrasound examination. Genetic analyses of the polymorphism rs5498 of the ICAM-1 gene were made by RT-PCR. RESULTS: The distribution of genotypes and frequencies of rs5498 polymorphism was not significantly different between the group with type 2 diabetes ( T2DM) and the control group. Genotype EE K469E polymorphism is associated with a statistically significant annual plaques growth. CONCLUSION: The EE genotype of the rs5498 of the ICAM-1 gene was associated with a more rapid progression of carotid atherosclerosis in patients with T2DM in comparison with other genotypes.

Polymorphisms of the peroxisome proliferator-activated receptor-γ (rs1801282) and its coactivator-1 (rs8192673) are associated with obesity indexes in subjects with type 2 diabetes mellitus.

UNLABELLED: The aim of this study was to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PGC-1α) gene (rs8192673) are associated with obesity indexes (BMI, waist circumference) in subjects with type 2 diabetes mellitus (T2DM) in Caucasian population. The second aim was to find an association of both polymorphisms with T2DM. METHODS: Two exonic SNPs of both genes rs1801282 of the PPAR-γ gene and rs8192673 of the PGC-1α gene) were genotyped in 881 unrelated Slovene subjects (Caucasians) with T2DM and in 348 subjects without T2DM (control subjects). RESULTS: Female homozygotes with the CC genotype of the rs8192673 had higher waist circumference in comparison with subjects with other genotypes. Homozygotes (females, males) with wild allele (Pro) of the rs1801282 (Pro12Ala polymorphism) had higher waist circumference in comparison with subjects with other genotypes. In the study, there were no differences in the distributions of the rs8192673 and the rs1801282 genotypes between patients with T2DM and controls. Linear regression analyses for both polymorphisms were performed and demonstrated an independent effect of the rs1801282 of the PPAR-γ on waist circumference in subjects with T2DM, whereas an independent effect on waist circumference was not demonstrated for the rs8192673 of the PGC-1α gene. CONCLUSIONS: In a large sample of the Caucasians the rs8192673 of the PGC-1α gene and the rs1801282 of the PPAR-γ gene were associated with waist circumference in subjects with T2DM.

Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 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. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM.

Polymorphisms of the PPAR-γ (rs1801282) and Its Coactivator (rs8192673) Have a Minor Effect on Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

Background. The present study was designed to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PGC-1α) gene (rs8192673) are associated with markers of carotid and coronary atherosclerosis in Caucasians with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled in the cross-sectional study. Markers of carotid atherosclerosis were assessed ultrasonographically. In 215 out of 595 subjects with T2DM, a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of either rs1801282 or rs8192673 was performed using KASPar assays. Results. In our study, we demonstrated an effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM in univariate and in multivariable linear regression analyses. Finally, we did not demonstrate any association between either rs1801282 or rs8192673 and markers of coronary atherosclerosis. Conclusions. In our study, we demonstrated a minor effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM. Moreover, we demonstrated a minor effect of the rs8192673 on CIMT progression in the 3.8-year follow-up in Caucasians with T2DM.

Carotid intima media-thickness and genes involved in lipid metabolism in diabetic patients using statins--a pathway toward personalized medicine.

The prognostic importance of large artery structure and function in relation to cardiovascular morbidity and mortality, together with the identification of new genetic risk factors have been two major areas of investigation in recent years. Carotid intima-media thickness (CIMT), as measured by B-mode ultrasound, is a surrogate marker for atherosclerosis and can be used to detect an accelerated disease process as well as subclinical disease. However, the genetic basis for CIMT variation is almost unknown. Cardiovascular genetics has led to numerous clinical studies generally focused on only one candidate gene and were frequently conducted in subjects with cardiovascular diseases and/or taking drugs that could affect CIMT. Pharmacogenetics is the study of the effect of a medication as it relates to single or defined sets of genes. An important goal of pharmacogenetics in cardiovascular disorders is to integrate the two (drugs plus genes) so that true personalized therapy can be delivered. In this paper, we will discuss the interaction between genes involved in lipid metabolism and statin therapy that affects intermediate phenotype (plasma lipid levels) and CIMT in patients with type 2 diabetes.