👤 Majid Ghayour-Mobarhan

Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases that result from the accumulation of excess triglycerides in the liver, and which, in its early phases, is categorized NAFLD, or hepato-steatosis with pure fatty liver. The mortality rate of non-alcoholic steatohepatitis (NASH) is more than NAFLD; therefore, diagnosing the disease in its early stages may decrease liver damage and increase the survival rate. In the current study, we screened the gene expression data of NAFLD patients and control samples from the public dataset GEO to detect DEGs. Then, the correlation betweenbetween the top selected DEGs and clinical data was evaluated. In the present study, two GEO datasets (GSE48452, GSE126848) were downloaded. The dysregulated expressed genes (DEGs) were identified by machine learning methods (Penalize regression models). Then, the shared DEGs between the two training datasets were validated using validation datasets. ROC-curve analysis was used to identify diagnostic markers. R software analyzed the interactions between DEGs, clinical data, and fatty liver. Ten novel genes, including ABCF1, SART3, APC5, NONO, KAT7, ZPR1, RABGAP1, SLC7A8, SPAG9, and KAT6A were found to have a differential expression between NAFLD and healthy individuals. Based on validation results and ROC analysis, NR4A2 and IGFBP1b were identified as diagnostic markers. These key genes may be predictive markers for the development of fatty liver. It is recommended that these key genes are assessed further as possible predictive markers during the development of fatty liver. Show less

Metabolic syndrome (MetS) is characterized by a clustering of cardiovascular risk factors that include: abdominal obesity, dyslipidemia, hypertension and glucose intolerance. Angiopoietin-like protein 4 (ANGPTL4) is a circulating peptide that is an inhibitor of lipoprotein lipase, a key enzyme in lipid metabolism. The objective of this study was to investigate the association of ANGPTL4 gene variants (E40K) with fasting serum triglyceride levels and with cardiovascular risk factors, that included the presence of MetS in 817 subjects recruited from the Mashhad stroke and heart Atherosclerosis Disorders (MASHAD) cohort Study. ANGPTL4 genotypes were determined using a TaqMan genotyping based real time PCR method. The association of the genetic variant with the risk of metabolic syndrome and its relationship with lipid profile were determined. The frequency of GG, GA and AA genotypes were 96.9, 2.7 and 0.4% in individuals with MetS, and 78.8, 20.8, 0.4%, in those without MetS. The GA genotype of the rs116843064 polymorphism was associated with a lower risk for MetS (e.g., OR in Codominant genetic model: 0.14, 95% CI: (0.06-0.33), p < 0.0001). Subject with an A allele had a higher risk for MetS (OR: 6.72, 95% CI: (3.05-14.82), p < 0.0001). There was a significant difference in fasted lipid profiles across the genotypes for ANGPTL4. Carriers of the AG genotype had higher levels of serum HDL-cholesterol (HDL-C) and lower TG, compared to the GG homozygotes genotype. The G allele at the rs116843064 polymorphic locus of the ANGPTL4 gene was associated with a lower prevalence of MetS. Show less

Recent genome-wide association studies (GWAS) have identified several genetic variants that influence the risk of dyslipidemia and coronary artery disease (CAD). In this study, we have examined the potential association of five SNPs variants related to lipid pathway, previously identified in GWAS studies (ZNF259 C>G, CETP I405VA/G, LPA C>T, LPLS447X and PSRC1 A>G) with CAD. Two hundred and ninety subjects including 194 patients with coronary artery disease and 96 controls were enrolled, followed by the analyses of anthropometric/biochemical parameters. Genotyping was carried out using Taq-Man real-time PCR based method. The association of the genetic polymorphisms with CAD was determined using univariate and multivariate analyses. CAD patients had a higher (p < 0.05) fasting blood glucose (FBG), total cholesterol (TC), high sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C) and waist circumference. Results showed that subjects with CETP rs5882 genetic variant, AA&AG genotypes, had a higher risk of developing Coronary artery disease [OR: 2.1, 95% CI (1.2-4.1), p value = 0.015]. Also subjects who carried the G allele of the ZNF259 polymorphism were at an increased the risk of developing CAD [OR 1.86, 95% CI: 1.06-3.25, p value = 0.029] and had an increased TC, LDL and TG levels (p < 0.05). Furthermore, no statistically significant association was found between genetic polymorphisms of PSRC1 A>G, LPL S447X and LPA C>T and CAD. We identified a relationship between a genetic variant in CETP and ZNF259 gene with CAD and CAD and lipid profile, respectively. Further investigation in a larger population may help to investigate the value of emerging marker as a risk stratification marker in CAD and its risk factors. Show less

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. 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. Serum CETP levels were not significantly altered among patients receiving curcumin. Curcumin and its complex had no significant effect on serum CETP concentrations. Show less

Obesity is a multifactorial disorder due to the complex interaction between genetic and environmental factors. Liver X receptor alpha (LXRα), encoded by the gene NR1H3, is involved in lipoprotein metabolism and its genetic variations may also play a role in the aetiology of obesity. To assess the association of two NR1H3 polymorphisms (rs11039155 and rs2279238) and their haplotypes with obesity in an Iranian population. A total of 447 unrelated subjects (including 206 overweight, 162 obese and 79 controls) were enrolled in the study and were genotyped by TaqMan assay using DNA from peripheral blood. The association of these two LXRα polymorphisms with the presence of obesity and overweight was assessed. There was no significant association between the two SNPs and obesity, even after adjustment for age and sex. By logistic regression using a dominant model, the odds ratios for obesity were: 1.32 (0.85-2.74) for rs11039155 and 0.77 (0.30--1.99) for rs2279238. Haplotype analyses identified three common haplotypes GC, GT and AC with frequency greater than 1%, but none of the haplotypes was associated with the risk of obesity. This study revealed that there was no significant association between LXRα polymorphisms and the presence of obesity in an Iranian population and suggests that these two SNPs are not major contributors to obesity risk in this population. Show less

The metabolic syndrome (MetS) is considered to be a major risk factor for type 2 diabetes mellitus and cardiovascular diseases. It is characterized by central adiposity, high blood pressure, glucose intolerance and abnormalities of lipoprotein metabolism. The cause of MetS is likely to be due to a complex interaction between genetic and environmental factors. Liver X receptors alpha (NR1H3) and beta (NR1H2) play a key role in lipid and carbohydrate metabolism. The aim of this study was to investigate the contribution of genetic polymorphisms in the LXRs to risk of MetS and related traits. Two common SNPs in NR1H3 (rs11039155 and rs2279238) and in NR1H2 (rs17373080 and rs2695121) were genotyped using TaqMan assays in MetS patients (n=265) and controls (n=219). Logistic regression analyses were performed to calculate the odds ratios (ORs) as a measure of association of genotypes with the presence of MetS and related phenotypes. Although The NR1H2 polymorphism rs2695121 was nominally associated with MetS but correction for multiple-testing and adjustment for age, sex and number of MetS criteria, failed to identify any significant interactions associated with prevalence of MetS. However in the haplotype analysis, a LXRα haplotype AC, was more common in controls and was associated with a significant protective effect for MetS (OR [95% CI]=0.25 [0.07-0.88], p=0.031). In conclusion, this study suggests that the above-named variants in LXRα and LXRβ genes are not potential contributors to the risk of MetS and related traits in an Iranian population. Show less