Cholesteryl ester transfer protein Taq1B polymorphism in an angiographically assessed Turkish population: no effects on coronary artery disease risk.

BACKGROUND: Taq1B polymorphism of cholesteryl ester transfer protein (CETP) is believed to associate with high-density lipoprotein-cholesterol (HDL-C) levels and may alter the susceptibility to atherosclerosis. AIM OF THE STUDY: This study investigated the effects of Taq1B polymorphism on HDL-C and coronary artery disease (CAD) risk in angiographically defined CAD patients. METHODS: One hundred thirty-five CAD patients and 112 healthy controls were screened for the CETP Taq1B genotype and plasma lipids. RESULTS: The genotype frequency of CAD patients and controls were similar. The HDL-C levels of all genotypes in the CAD group were significantly lower than the corresponding controls. Smoking and plasma triglycerides were the predictors of the HDL-C level in B1B1 bearers, whereas the subjects with a polymorphic B2 allele were affected by smoking and sex. CONCLUSION: CETP Taq1B polymorphism neither plays a role in determining HDL-C levels nor is a useful predictor of the risk of CAD.

Association of cholesteryl ester transfer protein -629C > A polymorphism with high-density lipoprotein cholesterol levels in coronary artery disease patients.

In Turkish population, plasma HDL-C levels were found to be lower than in any other country and it is suggested that this is associated with genetic origin. The cholesteryl ester transfer protein (CETP) -629C > A polymorphism is associated with lower plasma CETP concentration, with increased HDL-C level. In the present study, the frequency of -629C > A polymorphism in patients with coronary artery disease (CAD) was investigated and the effect of genotype on HDL-C was evaluated in a Turkish population. For this aim CETP -629C > A polymorphism was studied in angiographically documented CAD patients and healthy controls. There was no statistical significance in the distribution of genotypes between patients and controls. Although A allele carriers with CAD had significantly lower HDL-C levels than controls, plasma lipid levels showed no difference according to the genotypes. Adjustment by a logistic regression model predicting CAD status through HDL-C and including some risk factors as covariate indicated that the HDL-C doesn't have a significant association with CAD risk in CA and AA genotype carriers. Smoking, gender and hypertension were the common predictors for the HDL-C levels in CA and AA carriers. Although HDL-C appeared to be the only significant predictor of CAD in our study groups, the contribution of CETP -629C > A polymorphism to the alterations in HDL-C level appears to be weak to mention a protective effect of this polymorphism for CAD. In conclusion, the findings of the present study indicate that the CETP -629C > A polymorphism is not among the determinants of the coronary artery disease in Turks.

Increased plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in patients with angiographically defined coronary artery disease.

We investigated the oxidative modifications of lipids, proteins and DNA, three potential molecular targets of oxidative stress, in 30 patients with angiographically defined coronary artery disease (CAD) and 30 healthy control subjects. In addition, we examined relationships between these oxidative modifications and the severity of vascular lesions in patients with CAD. Malondialdehyde (MDA) and protein carbonyl (PC) levels, as well as ferric reducing antioxidant power (FRAP), were measured in the plasma. DNA damage was evaluated as single strand breaks (SSBs), formamidopyrimidine glycosylase (Fpg) and endonuclease III (E-III)-sensitive sites by the comet assay in DNA isolated from lymphocytes. MDA and PC levels increased, but FRAP values decreased, in patients as compared to controls. However, these values did not vary with the number of affected coronary vessels and were not correlated with Duke score, a parameter of the severity of vascular lesions in patients with CAD. We also found that lymphocyte DNA damage (SSBs, Fpg and E-III sites) were increased in patients. Although there were no significant differences in SSBs values in patients grouped according to affected vessel number, Fpg and E-III sites increased. We also detected significant correlations between Duke scores and SSBs and Fpg sites. Serum cholesterol, triglyceride and LDL-cholesterol levels were found to increase, but HDL-cholesterol levels decreased in CAD patients, but these lipids were not correlated with Duke scores. The results of this study reinforce the presence of increased combined oxidative modifications in lipid, protein and DNA in patients with CAD. However, lymphocyte DNA damage seems to be a more reliable assay than MDA and PC determinations to detect the severity of vascular lesions in patients.

Molecular correlates of temporomandibular joint disease.

OBJECTIVE: The relation between disease severity and the known mediators of pain, inflammation, and tissue damage-prostaglandin E 2 (PGE 2 ), leukotriene B 4 (LTB 4 ), malondialdehyde (MDA), nitric oxide (NO), and myeloperoxidase (MPO)-was examined in the synovial fluid of patients with internal derangement (ID) of the temporomandibular joint (TMJ). STUDY DESIGN: Thirty-two patients with ID were classified according to Wilkes by clinical and radiological examinations, and TMJ synovial fluid samples were obtained by arthrocentesis. PGE 2 and LTB 4 levels were measured by ELISA kits, MDA levels were determined by a fluorometric method, myeloperoxidase activity was determined by an end-point method, and NO levels were measured by Griess reaction. RESULTS: The earliest significant increase was observed in NO levels (stage II) and this elevation persisted in the subsequent stages. The first significant elevation in PGE 2 and LTB 4 levels and MPO activity were observed in stage III. Both PGE 2 and LTB 4 levels were increased in stage III and were correlated with each at this stage and in the subsequent stage. Significant increases in MDA levels were observed only in stage IV. At stage IV there was correlation between MDA and PGE 2 , MDA and LTB 4 , and MDA and MPO. The relation between PGE 2 and MDA was the most powerful one. CONCLUSION: Results of this cross-sectional study point out the relation between disease severity and levels of some molecular mediators in synovial fluid of TMJ. Longitudinal studies are needed to explore the role of these molecular mediators in the progression of ID.

Age-related increases in plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in elderly subjects.

OBJECTIVES: Increased oxidative stress has been hypothesized to play an important role in the aging process. A role for oxidative damage in normal aging is supported by studies in experimental animals, but there is limited evidence in humans. To investigate the relationship between the oxidative stress and aging in humans, we determined lipid and protein oxidation in plasma as well as DNA damage in lymphocytes in young and elderly subjects. DESIGN AND METHODS: 55 healthy subjects were divided into young (21-40 years) and elderly (61-85 years) groups. Plasma malondialdehyde (MDA), protein carbonyl (PC) levels, and grade of DNA damage in lymphocytes using comet assay as well as total ferric reducing antioxidant power (FRAP) in plasma were determined in young and elderly subjects. RESULTS: Plasma MDA and PC levels were found to be increased in plasma of elderly subjects as compared to young subjects. Increases in endogenous and H2O2-induced DNA damage were also observed in lymphocytes of elderly subjects. In addition, we detected a significant decrease in FRAP values in elderly subjects. Plasma MDA, PC levels and endogenous and H2O2-induced DNA damage were positively correlated with aging, but negatively with FRAP values. CONCLUSION: We evaluated MDA, PC levels and lymphocyte DNA damage altogether in both young and elderly subjects for the first time. The results of this study strongly support the presence of increased oxidative stress in elderly subjects.

Increased lipid peroxidation in serum and low-density lipoproteins associated with aging in humans.

This study was carried out in 140 healthy subjects who were divided into three subgroups of age: young (21-40 years), mature (41-60 years), and elderly (61-85 years) to investigate lipid peroxides and the antioxidant system in serum and low-density lipoproteins (LDL). Serum levels of cholesterol and LDL-cholesterol increased with age. The elderly group was found to have higher polyunsaturated fatty acid (PUFA) levels, thiobarbituric acid reactive substances (TBARS), diene conjugates, and lower cholesterol-adjusted vitamin E levels and antioxidant activity (AOA) as compared to the young group. No age-related difference was detected in serum vitamin C levels. Age correlated positively with serum cholesterol, LDL-cholesterol, PUFA, TBARS, diene conjugates, and negatively with cholesterol-adjusted vitamin E levels and AOA. In addition, endogenous LDL diene conjugate levels and the susceptibility of LDL to copper-induced lipid peroxidation increased in elderly subjects as compared with young subjects. In addition, positive correlations were detected between age and LDL endogenous diene conjugate levels and TBARS formation after copper incubation. However, the susceptibility of whole serum to copper-induced lipid peroxidation did not change in young and elderly subjects. Our results show that endogenous lipid peroxide levels in serum and LDL, and the susceptibility of LDL to copper-induced oxidation, increased with aging in humans.

The investigation of prooxidant-antioxidant balance in serum of children with family histories of essential hypertension.

It has been accepted that essential hypertension is associated with a loss of the balance between prooxidation and antioxidation. Thus, excessive oxygen free radical production may be an early event in the pathogenesis of hypertension. To compare lipid peroxidation and antioxidant system in serum of children of essential hypertensive and normotensive parents. Serum malondialdehyde (MDA) levels were measured spectrofluorometrically. Antioxidant activity, glutathione peroxidase, selenium levels in serum were measured as indices of antioxidant power. The peroxidation of apo B containing lipoproteins (VLDL+LDL) was measured as the susceptibility to oxidation in vitro. Serum MDA levels increased, but no marked differences in total antioxidant activity, glutathione peroxidase activity, selenium levels and VLDL+LDL oxidation were found in serum of children with family histories of essential hypertension as compared to children of normotensive parents.