The Association Between rs1748195 and rs11207997 Variants of the ANGPTL3 Gene and Susceptibility to Cardiovascular Disease in the MASHAD Cohort Study.

There is a strong genetic predisposition to cardiovascular disease (CVD). Loss-of-function variants of the angiopoietin-like 3 (ANGPTL3) gene have been reported to be associated with several lipid-related CVD risk factors that include serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) level, and total cholesterol (TC). We aimed to determine the association of two genetic variants, rs1748195 and rs11207997, of the ANGPTL3 locus and CVD risk in the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. The participants were 1002 individuals in the MASHAD cohort, with or without CVD, during the 6 years of follow-up. The subjects were categorized into two groups according to serum HDL concentration. DNA was extracted by the routine salting-out method, and genotyping of rs1748195 and rs11207997 variants of the ANGPTL3 gene was performed using the ARMS PCR method. Univariate and multivariate statistical analysis was used to assess the two gene variants' association with incident CVD and baseline lipid profile. There was a significant relationship between rs1748195 GG genotype and CVD risk in the individuals with a normal serum HDL-C. There was a significant association between the CT genotype of the rs11207997 polymorphism and CVD risk in individuals with a low serum HDL-C. Furthermore, carriers of the GG genotype of the rs1748195 and CT genotype of rs11207997 variant of ANGPTL3 had a higher risk of developing CVD disease. We have shown that the 1748195(GG) and 11207997(CT) gene variants of the ANGPTL3 locus are associated with an increased risk of CVD in an Iranian population sample.

Age and sex-specific reference intervals for prooxidant-antioxidant balance, anti-heat-shock protein 27 (anti-hsp27), and routine laboratory tests in the middle-aged adult population.

INTRODUCTION: We aimed to define specific reference intervals (RIs) for 11 biomarkers including inflammatory and oxidative stress biomarkers, liver, and renal function tests in a healthy Iranian adult population for the first time. METHODS: CLSI Ep28-A3 guidelines were then used to calculate accurate age- and sex- as well as body mass index (BMI)-specific RIs. RESULTS: RIs for studied biomarkers showed no significant age and sex-specific differences, except for uric acid, which had higher concentrations in men when compared to women. Additionally, after partitioning the participants based on the BMI with a cutoff point of 25 kg/m2 , only the levels of hs-CRP were positively associated with higher BMI (RI for BMI>25: 0.51-7.85 mg/L and for BMI<25: 0.40-4.46 mg/L). RI for PAB and anti-hsp-27 were reported 4.69-155.36 HK and 0.01-0.70 OD in men and women aged 35-65 years old. CONCLUSION: Partitioning by sex and BMI was only required for uric acid and hs-CRP, respectively, while other biomarkers required no partitioning. These results can be expected to valuably contribute to improve laboratory test result interpretation in adults for improved monitoring of various diseases in the Iranian population.

Association of ANGPTL3 polymorphisms with high-density lipoprotein cholesterol uptake capacity in patients with cardiovascular disease.

INTRODUCTION: Previous studies have shown the importance of angiopoietin-like 3 (ANGPTL3) as a modulator of lipid profiles. Cholesterol uptake capacity (CUC) is one means for assessing high-density lipoprotein (HDL) functionality. This study for the first time has investigated the relationship between genetic ANGPTL3 polymorphism and CUC in patients with cardiovascular disease. METHODS: Five hundred three subjects comprising 350 healthy subjects and 153 individuals who developed a cardiovascular disease (CVD) event during follow-up were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. A modified CUC method was used to determine the CUC of serum samples. Applied amplification refractory mutation system PCR was performed for ANGPTL3 variants genotyping including: rs10789117, rs1748195, and rs11207997. Sanger sequencing was applied to confirm the genotypes. RESULTS: The results showed that there was a significant relationship between the rs1748195 genotypes and HDL concentration in the CVD group (p = 0.02). Moreover, individuals with a GG genotype of the rs1748195 were associated with a lower risk of CVD (OR = 0.49, 95% CI = 0.24-0.98, p = 0.04) compared with CC genotype in the CUC ≤ 1.7 a.u subgroup. Moreover, the CT genotype of rs11207997 was associated with a lower risk of CVD (OR = 0.74, 95% CI = 0.41-1.3, p = 0.01) compared with CC genotype in CUC > 1.7 a.u subgroup. CONCLUSION: The results showed that the CT genotype of the rs11207997 variant was associated with a lower risk of incident CVD in patients with higher HDL functionality. As well, the rs1748195 gene variant may contribute to a reduced risk of CVD.

The Effects of Curcumin on Serum Heat Shock Protein 27 Antibody Titers in Patients with Metabolic Syndrome.

Metabolic syndrome (MetS) is associated with an increased risk of cardiovascular disease and diabetes mellitus. Inflammation and oxidant stress are features of MetS that can enhance the expression and release of heat shock proteins (Hsps), including the small heat shock protein, Hsp 27, and that may subsequently lead to the production of Hsp27 antibodies (anti-Hsp 27). Curcumin is an anti-inflammatory and antioxidant phytochemical that may ameliorate these features of MetS. We investigated the effects of unformulated curcumin and phospholipidated curcumin on antibody titers to heat shock protein 27 (anti-Hsp 27) in patients with MetS. A randomized double-blind, placebo-controlled clinical trial design was used in 120 patients with MetS (diagnosed according to the International Diabetes Federation [IDF] criteria). Participants were randomly allocated to 3 groups, with 40 individuals per group, that received either 1 g/d curcumin, phospholipidated curcumin, or a placebo for 6 weeks. The changes in serum concentrations of anti-Hsp 27 did not differ significantly between study groups (p = .283). There was no significant difference between baseline and end-of-trial concentrations of anti-Hsp 27 in groups supplemented with curcumin (p = .177), phospholipidated curcumin (p = .798), or placebo (p = .663). Curcumin supplementation (1 g/d) has no significant effects on anti-Hsp 27 titers in patients with MetS.

The effects of curcumin and a modified curcumin formulation on serum Cholesteryl Ester Transfer Protein concentrations in patients with metabolic syndrome: A randomized, placebo-controlled clinical trial.

OBJECTIVE: Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl ester from HDL-C to LDL-C and VLDL-C. The aim of the present trial was to evaluate the effect of curcumin and its modified formulation on serum CETP concentrations in patients with metabolic syndrome. MATERIALS AND METHODS: Participants were randomly allocated to one of three groups of 40 subjects receiving either unmodified curcumin or its phospholipid complex or placebo. Lipid profile and plasma CETP were measured at the start and six weeks after initiation of the treatment. The normality of data distribution was assessed by Kolmogorov-Smirnov test. Wilcoxon test was used for comparing the data before and after the intervention. The percent changes of CETP and biochemical factors among the three groups were compared using Kruskal-Wallis test. RESULTS: Serum CETP levels were not significantly altered among patients receiving curcumin. CONCLUSION: Curcumin and its complex had no significant effect on serum CETP concentrations.

The Effects of Curcumin and Curcumin-Phospholipid Complex on the Serum Pro-oxidant-Antioxidant Balance in Subjects with Metabolic Syndrome.

Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro-oxidant-antioxidant balance (PAB) in patients with MetS. This double-blind, randomized, placebo-controlled trial was conducted over 6 weeks. Subjects (n = 120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1 g/day of simple curcumin, the phospholipidated curcumin group received 1 g/day of phospholipidated curcumin (containing 200 mg of pure curcumin), and the control group received 1 g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6 weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p < 0.001), but in the phospholipidated curcumin group, elevation of PAB level was not significant (p = 0.053). The results of our study did not suggest any improvement of PAB following supplementation with curcumin in MetS subjects. Copyright © 2017 John Wiley & Sons, Ltd.

Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: A sex-stratified analysis in a population-based study.

BACKGROUND: Depression and anxiety are two common mood disorders that are both linked to systemic inflammation. Increased white blood cell (WBC) count and red cell distribution width (RDW) are associated with negative clinical outcomes in a wide variety of pathological conditions. WBC is a non-specific inflammatory marker and RDW is also strongly related to other inflammatory markers. Therefore, we proposed that there might be an association between these hematological inflammatory markers and depression/anxiety symptoms. OBJECTIVE: The primary objective of this study was to examine the association between depression/anxiety symptoms and hematological inflammatory markers including WBC and RDW in a large population-based study. METHODS: Symptoms of depression and anxiety and a complete blood count (CBC) were measured in 9274 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventories. RESULTS: The mean WBC count increased with increasing severity of symptoms of depression and anxiety among men. Male participants with severe depression had significantly higher values of RDW (p<0.001); however, this relationship was less marked among women (p=0.004). In addition, men (but not women) with severe anxiety symptoms had significantly higher values of RDW (p<0.001). Moreover, there was a negative association between red blood cell (RBC) and mean corpuscular hemoglobin (MCH) and symptoms of depression/anxiety. CONCLUSION: Our results suggest that higher depression and anxiety scores are associated with an enhanced inflammatory state, as assessed by higher hematological inflammatory markers including WBC and RDW, even after adjusting for potential confounders.

Effects of Curcumin on Serum Vitamin E Concentrations in Individuals with Metabolic Syndrome.

Vitamin E is an important lipid-soluble antioxidant. The aim of the present study was to investigate the effect of curcumin on serum vitamin E levels in subjects with metabolic syndrome (MetS). A total of 120 subjects aged 18-65 years old with MetS were recruited in this study according to the International Diabetic Federation Criteria. Included subjects were randomized into three groups: subjects receiving lecithinized curcumin (1 g/day equivalent to 200-mg pure curcumin per day) for a period of 6 weeks )n = 40), patients receiving unformulated curcumin (1 g/day) for a period of 6 weeks )n = 40) and a control group receiving placebo for the same period (n = 40). Vitamin E was determined in all patients before and after the intervention using high-performance liquid chromatography method. Results showed that curcumin has no improving effect on serum levels of vitamin E (p > 0.05). There were significant differences between pre-trial and post-trial levels of vitamin E/low-density lipoprotein cholesterol ratio (p < 0.05), vitamin E/high-density lipoprotein cholesterol ratio (p < 0.05), vitamin E/total cholesterol ratio (p < 0.01) and vitamin E/triglyceride ratio (p < 0.05) between the three groups of the study. Results of the present study did not suggest any improving effect of curcumin supplementation on serum vitamin E concentrations in subjects with MetS. Copyright © 2017 John Wiley & Sons, Ltd.