S-Allylcysteine, a garlic compound, increases ABCA1 expression in human THP-1 macrophages.

ATP-binding cassette transporter A1 (ABCA1) is a key mediator of cholesterol efflux to apoA-I in lipid-loaded macrophages, which is the first step of reverse cholesterol transport in vivo and a critical step in preventing atherosclerosis. Enhanced ABCA1 expression may inhibit foam cell formation and consequently reduce atherogenic risk. The purpose of this study was to investigate the effect of S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract, on the expression of ATP-binding cassette transporter A1 in human THP-1 macrophages. The human monocyte THP-1 cells were differentiated to macrophage cells in the presence of phorbol 12-myristate13-acetate (PMA). Macrophage cells were then treated with different concentrations (10, 20 and 40 mM) of SAC for 24 h. Total RNA of treated macrophages was extracted and analyzed with real-time RT-PCR. ABCA1 protein expression was also analyzed with western blotting. Results showed that SAC increased the ABCA1 mRNA (1.82-, 2.07- and 2.23-fold) and protein (1.37-, 1.55- and 2.08-fold) expression in macrophage THP-1 cells compared with control (untreated cells). Results suggested that SAC can increase ABCA1 expression in macrophages and may be beneficial in promoting reverse cholesterol efflux.

Polyunsaturated fatty acids and modulation of cholesterol homeostasis in THP-1 macrophage-derived foam cells.

Transformation of macrophages to foam cells is determined by the rates of cholesterol uptake and efflux. This study uses a real time RT-PCR technique to investigate the role of conjugated linoleic acid (CLA), α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) in the regulation of the ATP-binding cassette A1 (ABCA1) and liver X receptor α (LXR) genes, which are involved in cholesterol homeostasis. Accordingly, these fatty acids significantly reduced the total, free and esterified cholesterols within the foam cells. While the expression of the ABCA1 and LXRα genes was increased in the presence of the pharmacological LXRα ligand, T0901317, their mRNA expression was not significantly affected by CLA, ALA and EPA. These results suggest that although polyunsaturated fatty acids have an effect on cholesterol homeostasis, they cannot change the expression of the ABCA1 and LXRα genes. Alternatively, several other genes and proteins may be involved.

Association of cys 311 ser polymorphism of paraoxonase-2 gene with the risk of coronary artery disease.

BACKGROUND: Recently another member of the paraoxonase gene family designated paraoxonase-2 has been identified. Paraoxonase-2 has antioxidant properties similar to paraoxonase-1 and paraoxonase-3. However, in contrast to paraoxonase-1 and paraoxonase-3, paraoxonase-2 is not associated with high-density lipoprotein and may only exert its antioxidant function at the cellular level. METHODS: We assessed the frequency and genotype distribution of cys 311 ser paraoxonase-2 polymorphism in 300 subjects (>40 years old) with angiographic documentation of coronary artery disease (150 patients with >50% stenosis served as cases and 150 individuals with <20% stenosis served as controls) to determine the possible association between this mutation and susceptibility for coronary artery disease. The paraoxonase-2 genotypes were determined by polymerase chain reaction and DdeI restriction enzyme digestion. RESULTS: The cases (coronary artery disease positive patients) showed significant differences in the distribution of cys 311 ser paraoxonase-2 genotypes as compared with the controls (coronary artery disease negative subjects, P=0.015). The analysis of paraoxonase-2 genotypes distribution showed higher percentage of CC genotype among coronary artery disease positive compared with coronary artery disease negative (P=0.008). After controlling for other risk factors, the cys 311 ser polymorphism had not correlation with age, body mass index, gender, smoking, diabetes, level of high-density lipoprotein, low-density lipoprotein, triglyceride, and total cholesterol. CONCLUSION: Our data indicate a major effect of the paraoxonase-2 polymorphism on coronary artery disease risk in patients referred to Shariati Hospital in Tehran.

The status of biochemical parameters in varying degrees of vitamin D deficiency.

Vitamin D (Vit D) is an essential element for the regulation of serum calcium, phosphate, and alkaline phosphatase (Alk Ph). Because the Vit D serum level is not usually measured directly, Vit D deficiency is diagnosed indirectly by changes in serum calcium, phosphate, and Alk Ph leves. The current study assessed the status of these biochemical parameters in subjects with different degrees of Vit D deficiency. We selected 1,210 subjects, between 20 and 69 years old, randomly from the Tehran population. Subjects with diseases or medications that modified bone metabolism were excluded from the study. Serum 25(OH) D, calcium, phosphate, Alk Ph, and parathyroid hormone (PTH) levels were measured and the status of these biochemical parameters was compared in subjects with different degrees of Vit D deficiency. Vit D deficiency was diagnosed in 79.6% of the subjects. Different degrees of Vit D deficiency were classified as follows: group 1, severe; group 2, moderate; and group 3, mild. Serum PTH levels in the Vit D-deficient groups were significantly higher than that in group 4 (normal Vit D). Serum calcium and phosphate levels in groups 1 and 2 were significantly lower than those in groups 3 and 4. No significant difference was seen in serum Alk Ph in the groups with different degrees of Vit D deficiency. The sensivity for at least one biochemical variable (calcium, phosphorus, or Alk Ph) for the detection of severe, moderate, and mild Vit D deficiency was 24.2%, 13.8%, and 6%, respectively. When the serum 25(OH) D level was reduced to less than 25 nmol/l (groups 1 and 2), the effects of Vit D deficiency on calcium and phosphate levels were obvious. Therefore, the usual biochemical parameters (calcium, phosphate, Alk Ph) alone do not have sufficient sensitivity to detect mild deficiency of Vit D.

Association between apolipoprotein E polymorphism and Alzheimer disease in Tehran, Iran.

Epsilon 4 allele of apolipoprotein E (APOE-epsilon4) is a major risk factor for Alzheimer's disease (AD). The association of APOE allele frequencies with AD remains unknown in developing countries. We examined the frequency of APOE alleles in 105 patients with AD and 129 cognitively normal subjects of similar age and sex (control group), in Tehran, Iran. The APOE-epsilon4 allele frequency was significantly higher in the AD subjects than in the control group (21% versus 6.2%, p < 0.001). In addition, the OR for APOE-epsilon4 heterozygous and homozygous subjects were 3.2 (p = 0.001) and 12.75 (p = 0.01), respectively. The OR was not uniform across age groups. The AD subjects carrying one or two APOE-epsilon4 allele showed earlier age-at-onset (p < 0.001). These data suggest that the APOE-epsilon4 allele increase the risk for AD in Tehran population in a dose and age-dependent manner. Although the APOE-epsilon2 allele frequency was lower in the AD subjects than in the control group (0.95% versus 2.7%, p = 0.15), APOE-epsilon2 was not associated with the onset of AD in Tehran's population. The OR for epsilon2 allele in AD subjects was 0.34 (p = 0.21). The genotype frequencies for epsilon3, epsilon4, and epsilon2 alleles in control subjects were 91.2, 6.1, and 2.7%, respectively. These values were similar to that reported for Turkish, Greece, Japanese, Spanish, and Moroccan populations, but they were significantly different from the reported values for the other ethnic populations. This observation emphasizes the importance of geographical location and ethnical background of the subjects in the study of APOE genotypes and their association with AD.

Analysis of association between butyrylcholinesterase K variant and apolipoprotein E genotypes in Alzheimer's disease.

Recent studies indicate that there is a synergic association between butyrylcholinesterase-K variant (BChE-K) and apolipoproteinE-epsilon 4 (ApoE-epsilon 4) to promote risk for Alzheimer's disease (AD). Most subsequently replicative studies have been unable to confirm these finding. We attempted to replicate this finding in 105 AD cases and age and sex matched 129 controls from Tehran population, Iran. The BChE genotype of patients were found to be significantly different from controls (chi(2) = 12.2, d.f. = 2, p = 0.002). The frequency of BChE-K allele was also found to differ significantly in cases compared to controls [24% versus 12% (chi(2) = 20.6, d.f. = 2, p < 0.001)] leading to an increased risk of AD in subjects with this allele (OR = 2.5, 95% CI = 1.64-3.8, p = 0.001). This risk was found to increase from (OR = 2.37, 95% CI = 1.3-4.2, p = 0.006) in subjects less than 75 years old to (OR = 3.16, 95% CI = 1.41-7.1, p = 0.001) in subjects 75 years and older. But, the ApoE-epsilon 4 allele association risk was found to decrease from (OR = 9.5, 95% CI = 3.74-24.1, p = 0.001) in subjects <75 years to (OR = 1.36, 95% CI = 0.49-4.1, p = 0.58) in those subjects 75 years and older. Furthermore, we found a very strong synergic association between BChE-K and ApoE-epsilon 4 OR = 19.1 (95% CI = 428-85.45, p < 0.001). In spite of this, synergism decreased from OR = 36.2 (95% CI = 4.4-296, p = 0.001) in subjects <75 year olds to OR = 6.2 (95% CI = 0.9-72.4, p = 0.06) in subjects > or =75 years. We have found that BChE-K and ApoE-epsilon 4 alleles act synergistically to increase the risk of the late-onset AD, particularly in age group <75 years in Tehran, Iran.

Vitamin D deficiency and causative factors in the population of Tehran.

BACKGROUND: There are multiple studies in different countries regarding the prevalence of vitamin D deficiency. These studies showed high prevalence of vitamin D deficiency in Asian countries. This study tries to elucidate the prevalence of vitamin D deficiency and its influencing factors in population of Tehran. METHODS: 1210 subjects 20-64 years old were randomly selected. 25 (OH) D serum levels were measured. Duration of exposure to sunlight, the type of clothing and level of calcium intake and BMI were quantified based on a questionnaire. RESULTS: A high percentage of vitamin D deficiency was defined in the study population. Prevalence of severe, moderate and mild Vitamin D deficiency was 9.5%, 57.6% and 14.2% respectively. Vitamin D serum levels had no significant statistical relation with the duration of exposure to sunlight, kind of clothing and BMI. Calcium intake in the normal vitamin D group was significantly higher than the other groups (714.67 +/- 330.8 mg/day vs 503.39 +/- 303.1, 577.93 +/- 304.9,595.84 +/- 313.6). Vitamin D serum levels in young and middle aged females were significantly lower than the older group. CONCLUSIONS: Vitamin D deficiency has a high prevalence in Tehran. In order to avoid complications of vitamin D deficiency, supplemental dietary intake seems essential.