Association between the FABP2 Ala54Thr and CRP+1059C/G polymorphisms and small dense LDL level in patients with atherosclerosis: a case-control study.

BACKGROUND: The polymorphisms of fatty acid-binding protein 2 (FABP2) and C-reactive protein (CRP) might act as genetic risk factors for atherosclerosis. The study aimed to investigate the relationship between FABP2 Ala54Thr and CRP+1059C/G polymorphisms and atherosclerosis as well as the association of Small dense-LDL (sd-LDL). METHODS: A total of 255 subjects (125 controls and 130 patients) were included. The FABP2 and CRP polymorphisms were determined by PCR-RFLP and AS-PCR methods, respectively. Sd-LDL was measured based on Hirano et al method. RESULTS: There were no significant distinctions between the patient and control groups concerning FABP2 and CRP polymorphisms (p > .05). No significant relationship was observed between studied polymorphisms and sd-LDL level in the patient group (p > .05). However, patients group had higher level of sd-LDL compared to controls (p < .05). CONCLUSION: FABP2 Ala54Thr and CRP+1059G/C polymorphisms were not associated with atherosclerosis and sd-LDL level. However, the increased sd-LDL level was known as a risk factor for atherosclerosis.

Association of E-Selectin gene polymorphisms and serum E-Selectin level with risk of coronary artery disease in lur population of Iran.

BACKGROUND: Adhesion molecules like E-selectin have important role in pathogenesis of atherosclerosis. C1901T and G98T polymorphisms of E-selectin gene and E-selectin serum level may affect the risk of coronary artery disease (CAD). METHODS: A total of 145 normal individuals and 154 patients diagnosed with CAD from the Lur population of Iran undergoing coronary angiography were enrolled. Genetic polymorphisms of E-selectin were determined using PCR-RFLP. Serum level of soluble E-selectin was measured using Elisa. RESULTS: T allele in C1901T polymorphism was significantly associated with an increased risk of atherosclerosis (P = 0.018). No significant association was observed for G98T polymorphism. The mean serum level of soluble E-selectin in the patient group was significantly higher than the control group (P < 0.001). CONCLUSIONS: Allele type in C1901T polymorphism plays a role in increasing the risk of developing CAD. Furthermore, since serum E-selectin level is associated with systemic inflammation, it contributes to the increased risk of the disease.

Genetic associations and serum paraoxonase levels with atherosclerosis in western Iranian patients.

The oxidative modification of low-density lipoprotein (LDL) in the arterial wall plays a pivotal role in the initiation and progression of atherosclerosis which is a complex and progressive disorder. Paraoxonase1 (PON1), which is required for lipid metabolism, is believed to protect LDL from oxidation. The relationship between PON1 gene Leusin55Methionin (L55M) and Glutamine192Arginine (Q192R) polymorphisms in western Iranians with atherosclerosis and its association with enzyme activity and oxidized low-density lipoprotein (oxLDL) were examined in the present study. In this study, blood specimens were collected from 145 healthy individuals and 154 patients with atherosclerosis proven by angiography referred to Shahid Madani Hospital, Khorramabad, Iran. Genomic deoxy ribonucleic acid (DNA) was extracted from whole blood. For all the subjects, restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was carried out for the detection of L55M and Q192R polymorphisms. PON1 enzyme activity and the level of oxLDL were also evaluated. There was a 3.114-fold increase in the risk of developing atherosclerosis in the subjects presenting the PON1L55M, MM genotype compared to those with the LL genotype (OR 3.114; 95% CI 1.412-6.870). PON1Q192R polymorphism in the PON1 gene was not associated with atherosclerosis. Patients with atherosclerosis had significantly higher oxLDL and reduced PON1 enzyme activity (P < 0.05) compared to the controls. There was no association between the type of genotype, enzyme activity, and oxLDL level. It has been concluded that PON1L55M polymorphism and MM genotype are associated with an increased risk of coronary artery disease (CAD) in Iranian patients with atherosclerosis. We did not find any relationship between PON1Q192R polymorphism and atherosclerosis.

Study of angiotensin-converting enzyme insertion/deletion polymorphism, enzyme activity and oxidized low density lipoprotein in Western Iranians with atherosclerosis: a case-control study.

BACKGROUND: It has been indicated that Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) polymorphism (rs4646994) could be regarded as a genetic factor that raises the risk of CAD through its impact on the activity of Angiotensin-Converting Enzyme (ACE) and angiotensin II level. The present study seeks to examine the relationship between ACE I/D polymorphism with the risk of atherosclerosis. Moreover, its potential effects on ACE activity and oxLDL level are investigated. METHODS: In this study, 145 healthy individuals and 154 patients (143 males and 156 females) were selected among the subjects referred to Shahid Madani Hospital. Atherosclerosis was determined in all subjects with gold standard angiography. Blood samples were collected, used to isolate white blood cells (WBC) and serum separation. The DNA was extracted and the polymorphism was determined by polymerase chain reaction (PCR). The enzyme activity was measured using high-performance liquid chromatography (HPLC). RESULTS: This study indicated that patients with atherosclerosis had higher levels of oxidized Low-Density Lipoprotein (oxLDL) and ACE activity (P < 0.05) as compared to controls. Although we found a significant association between ACE I/D polymorphism genotype and the allele with atherosclerosis in the male group, there were no association when the entire patient group was compared to the entire control group. CONCLUSION: Our study revealed the ACE I/D polymorphism of the ACE gene may not be an independent risk factor in the development of atherosclerosis and evaluation of ACE activity level is more important in evaluating the risk of disease. The researchers found no relation between ACE I/D polymorphism and atherosclerosis and also between types of genotype, ACE activity, and OxLDL level.

The Relation between Polymorphisms in Exon 5 and Exon 6 of GSTP1 Gene and the Risk of Lung Cancer in Iranian People

Objective: The GSTP1 gene, which is located on chromosome 11q13, consists of 7 exons and 6 introns. There are two polymorphisms in GSTP1 that have been exposed to a transposition for codon 105 (Ile/Val) and 114 (Ala/Val) in exons 5 and 6, which have been studied previously in relation to lung cancer. Since the level of GSTP1 expression in lung tissues and other human epithelial tissues is high, GSTP1Val-105 polymorphism is recognized as a sensitive factor for tobacco-related cancers, especially lung cancer. Methods: One hundred and twenty tissue block samples of patients with lung cancers and 120 peripheral blood samples of the control group were obtained from two referral cancer centers in Tehran, Iran, from 2011 to 2016. Genomic DNA was extracted from tissue blocks and buffy coat of study cases to detect SNP of GSTP1 gene using Tetra-primer ARMS-PCR. Results: There was a notable correlation between the incidence of lung cancer and variant Val105 (P-value=0.001; OR=2/6; 95% CI=1.49-4.53) and Ile105 (P-value=0.003; OR=0.41; 95% CI=0.23-0.73). The odds ratio for lung cancer in the homozygous Ile105/Ile105 genotype was 3.56 times higher than that of individual with heterozygous Ile105/Val105 (P-value<0.001; OR=3/56; 95% CI=1.826-6.934) genotype, that was statistically significant. Furthermore, the results showed that there was no significant correlation between Ala114/Val114 genotypes and lung cancer. The BC (P-value=0.007; OR=0.16; 95% CI=0.04-0.61) and AA (P=0.001) genotypes were statistically significant (P-value <0.05); and for those who had AA genotype, the odds ratio was almost six times higher than those with BC genotype. Conclusions: The study of GSTP1 polymorphisms indicated that unlike the polymorphism in exon 5, the GSTP1 exon 6 polymorphism correlated with the lung cancer risk in the select group of Iranian people. Likewise, the potential use of this genetic polymorphism as a lung cancer predictor is confirmed.

Paraoxonase 1 Activity, Lipid Profile, and Atherogenic Indexes Status in Coronary Heart Disease.

BACKGROUND: Dyslipidemia is considered an independent risk factor for coronary heart disease (CHD). In the present study, we examined lipid profiles and paraoxonase 1 (PON1) activity and atherogenic indexes status and the relationship of PON1 activity by high-density lipoprotein (HDL) and atherogenic indexes in CHD patients and healthy people. METHODS: The aim of the study was to compare PON1, lipid profiles, and atherogenic indexes in CHD patients and healthy people as controls. This study enrolled 50 CHD patients and 50 matched healthy controls. Serum activities of PON1 and levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and atherogenic indexes were analyzed. Data were analyzed by unpaired Student's t tests. Coefficients of correlation were calculated using Pearson's correlation analysis. RESULTS: Levels of TG, TC, LDL, VLDL, FBG, and atherogenic indexes, atherogenic coefficients, and cardiac risk ratios were significantly greater in CHD patients than in controls. Paraoxonase 1 activity and HDL-C levels were significantly less in CHD patients than in controls. Also, PON1 activity correlated positively with HDLC and negatively with atherogenic coefficient, and cardiac risk ratios 1 and 2 in CHD patients. CONCLUSION: This study showed that CHD is associated with high lipid levels and atherogenic indexes, and low PON1 activity and HDL-C concentrations. Coronary heart disease is a pernicious disease requiring prolonged medical management and hypolipidemic drugs.

Protective effects of oleuropein against renal injury oxidative damage in alloxan-induced diabetic rats; a histological and biochemical study.

BACKGROUND: Oleuropein is a potent antioxidant and free-radical scavenger with antiinflammatory properties. OBJECTIVES: In the present study, we evaluated the protective effects of oleuropein on myeloperoxidase (MPO) activity, nitrite, urea, creatinine and glomerulosclerosis in alloxan-induced type 1 diabetic rats. MATERIALS AND METHODS: Thirty Sprague-Dawley male rats were randomly divided into 3 groups: group 1 as control; group 2 as untreated diabetic; and group 3 as treated with oleuropein 15 mg/kg i.p daily. Diabetes was induced in the second and third groups by subcutaneous alloxan injection. After 48 days, the animals were anaesthetized and then the livers and kidneys were removed immediately and used fresh or kept frozen until MPO activity analysis. Blood samples were also collected before sacrificing to measure nitrite, urea, and creatinine. Kidney paraffin sections were prepared to estimate glomerular volume, leukocyte infiltration, and glomerulosclerosis. RESULTS: Oleuropein significantly decreased leukocyte infiltration and glomerulosclerosis in the treated group compared with the diabetic untreated group. Oleuropein significantly decreased the levels of urea, nitrite, and creatinine in the treated group compared with the diabetic untreated group. Moreover, oleuropein significantly decreased MPO activity in the treated group compared with the diabetic untreated group. CONCLUSIONS: Oleuropein has antioxidative and antiatherogenic activities and exerts beneficial effects on inflammation and kidney function test and decreases diabetic complication in diabetic rats.

The effect of atorvastatin treatment duration on oxidative stress markers and lipid profile in patients with coronary artery diseases: A case series study.

BACKGROUND: The major aim of this study was evaluating the effect of atorvastatin treatment on thiobarbituric acid reactive substances (TBARS), ferric reducing the ability of plasma (FRAP), small dense low-density lipoprotein cholesterol (sdLDL) and lipid profile in coronary artery disease (CAD) patients. METHODS: This study was carried out on 83 patients with angiographically proven coronary artery stenosis (52 men and 31 women) at Shahid Madani Hospital, Khorramabad, Iran, in 2015. The patients were divided into the 3 groups. 27 patients were classified statins consumption less than 6 days, 28 patients for 6 to 90 days, and 28 patients for more than 90 days. The level of sdLDL, lipid profile, TBARS and FRAP were assayed. RESULTS: FRAP levels of patients that received atorvastatin for more than 90 days (832 ± 101) were significantly elevated (P = 0.01) compared to the patients received atorvastatin less than 6 days (688 ± 75), whereas the levels of TBARS diminished significantly (P = 0.04). Also, the levels of total cholesterol (TC) and LDL-C were significantly decreased after 3 months of atorvastatin receiving (158 as compared to patients that consumed atorvastatin less than 6 days), (P = 0.02 and 0.03, respectively). The level of sdLDL was slightly increased with long-time consumption of atorvastatin (37 ± 14) in patients in comparison with patients that received atorvastatin less than 6 days (32 ± 15) (P = 0.06), but was not significant. CONCLUSION: The serum level of TBARS decreased and the serum level of FRAP increased in patients with long-time receiving atorvastatin. Therefore, atorvastatin contributes to the lowering oxidative stress in these patients.

Biochemical effects of oleuropein in gentamicin-induced nephrotoxicity in rats.

BACKGROUND: Oleuropein is a natural antioxidant and scavenging free radicals. In the present study, we examined effect of oleuropein on the paraoxonase 1 (PON1) activity, lipid peroxidation, lipid profile, atherogenic indexes, and relationship of PON1 activity by high-density lipoprotein-cholesterol (HDL-C) and atherogenic indices in gentamicin (GM)-induced nephrotoxicity in rats. METHODS: This is a lab trial study in Khorramabad, Lorestan province of Iran (2013). 30 Sprague-Dawley rats were divided into three groups to receive saline; GM, 100 mg/kg/day; and GM plus oleuropein by 15 mg/kg intraperitoneal daily, respectively. After 12 days, animals were anesthetized, blood samples were also collected before killing to measure the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and very LDL (VLDL), HDL-C, atherogenic index, lipid peroxidation, and the activities of PON1 of all groups were analyzed. Data were analyzed, and P < 0.050 was considered significant. RESULTS: Oleuropein significantly decreased lipid peroxidation, TG, TC, LDL, VLDL, atherogenic index, atherogenic coefficient (AC), and cardiac risk ratio (CRR). HDL-C level was significantly increased when treated with oleuropein. The activity of PON1 in treated animals was (62.64 ± 8.68) that it was significantly higher than untreated animals (47.06 ± 4.10) (P = 0.047). The activity of PON1 in the untreated nephrotoxic rats was significantly lower than that of control animals (77.84 ± 9.43) (P = 0.030). Furthermore, the activity of PON1 correlated positively with HDL-C and negatively with AC, CRR 1, and CRR 2 in the treated group with oleuropein. CONCLUSION: This study showed that oleuropein improves PON1 activity, lipid profile, and atherogenic index and can probably decrease the risk of cardiovascular death in nephrotoxic patients.

Is the GSTM1 null polymorphism a risk factor for primary angle-closure glaucoma among Iranian population?

Glutathione S-transferases (GSTs) are members of multigenic family which have the essential functionin cells as an antioxidant. In the present study we studied the polymorphism of GSTT1 and GSTM1 deletion genotypes in Iranian patients with primary closed angle glaucoma (PCAG) compared to healthy subjects. We conducted a study of 41 PCAG patients (24 women, 17 men) and 100 healthy participants (57 women, 43 men) to determine the prevalence of GSTT1 and GSTM1 deletion genotypes and the risk of PCAG, which were determined by multiplex polymerase chain reaction. Genotypes of GSTM1 and GSTT1 null deletions were determined in 22 (53.7%) and 7 (17.1%) patients with PCAG and 34 (34%) and 15 (15%) in healthy participants. Comparison of patients and healthy ones regarding GSTM1 and GSTT1 genotypes revealed increase of GSTM1 null deletions genotypes' in patients with PCAG (P=0.03). It was concluded that the increased frequencies of GSTM1 null in patients with PCAG could be associated with a risk factor for incidence of PCAG in the Iranian population.

Glutathione s-transferase M1 and T1 genetic polymorphisms in Iranian patients with glaucoma.

OBJECTIVES: Glaucoma is the second leading cause of blindness and it is related to oxidative stress based on numerous studies. Glutathione S-transferases (GSTs) are members of multigenic family, which have important role in cells as an antioxidant. In the present study, we examined the polymorphism of GSTT1 and GSTM1 deletion genotypes (T0M1, T1M0, and T0M0) in 100 Glaucoma patients (41with primary open angle glaucoma (PCAG), and 59 with primary closed angle glaucoma (POAG)) compared to 100 healthy subjects. MATERIALS AND METHODS: GSTM1and GSTT1 polymorphisms were determined by multiplex polymerase chain reaction. RESULTS: GSTM1 and GSTT1 null deletions genotypes were determined in 22 (53.7%) and 7 (17.1%) patients with PCAG and 34 (34%) and 15 (15%) in healthy subjects. Comparison between patients and healthy subjects regarding GSTM1 and GSTT1 genotypes revealed increase of GSTM1 null deletions genotypes in patients with PCAG (P=0.03). CONCLUSION: It was concluded that the increased frequencies of GSTM1 null in patients with PCAG could be a risk factor for incidence of PCAG in the Iranian population.

Amelioration of lipid peroxidation in vivo and in vitro by Satureja khozestanica essential oil in alloxan-induced diabetic rats.

BACKGROUND: We examined possible protective effect of Satureja khozestanica essential oil (SKE) on in vivo and in vitro lipid peroxidation in alloxan-induced Type 1 diabetic rats. METHODS: Thirty Sprage-dawley male rats were divided into three groups randomly; group one as control, group two diabetic untreatment, and group three treatments with SKE by 500 ppm in drinking water, respectively. Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, animals were anaesthetized, livers and kidneys were then removed immediately and used fresh or kept frozen until their lipid peroxidation analysis. Lipid peroxidation was determined by measurement of thiobarbituric acid reactive substances (TBARS). Blood samples were also collected before killing to measure the levels of fasting blood suger (FBS) and lipid peroxidation. RESULTS: SKE significantly inhibited the levels of FBS, TBARS serum and kidney content in treated group compared with the diabetic untreated group. Also the levels of malonedialdehyde liver content unaltered in treated group. SKE significantly inhibited LDL oxidation in vitro. CONCLUSIONS: The findings showed that SKE exerts beneficial effects on the lipid peroxidation in alloxan-induced Type 1 diabetic rats.