👤 Yadollah Mehrabi

Anhedonia or inability to experience pleasure is the sign of various neuropsychiatric conditions. Current treatment options do not provide adequate control of anhedonia. The present study was conducted to evaluate the protective effects of valproic acid (VPA) as a nonspecific histone deacetylase (HDAC) inhibitor to reverse the effects of stress on induction of anhedonia and explore possible mechanisms. To induce anhedonia, a rat model of chronic unpredictable mild stress (CUMS) was established. Animals were assigned into no stress, stress (6 weeks of CUMS) and two treatment groups. VPA treatment was carried out for 4 continuous weeks (200 mg/kg/day). Behavioral assessments were performed using sucrose consumption (SCT) and new object recognition (NOR) tests. The expression of genes was evaluated using qRT-PCR. The cell density was determined using Nissl staining. Rats with CUMS showed depressive-like behaviors and impaired memory performance compared with the non-stressed group (p < 0.01). Moreover, they had significantly higher levels of HDAC3 and MC4R expression in the nucleus accumbens (NAc) compared to the non-stressed group (p < 0.01). The NAc cell density was significantly higher in the non-stressed rats (p < 0.05). Corticosterone plasma level was increased in the CUMS compared to the non-stressed group (p < 0.05). In the CUMS + VPA subgroup, the corticosterone (CORT) plasma level was lower compared with the CUMS + Saline and/or the CUMS groups (p < 0.05). These findings suggest that VPA can improve anhedonia and stress. Although the protective effect of VPA might link to decreasing HDAC3 and MC4R genes expression in NAc. Show less

A number of genome-wide association studies (GWASs) have identified several genetic determinants of plasma lipids in European populations, in which analytical approaches have often been based on the linear regression models and the association test between a SNP and each lipid component individually in cross-sectional designs. Since lipid variations are correlated, the consideration of pleiotropy is necessary and using methods that can perform simultaneous association test of multiple longitudinal traits provides more information about the recognition of the pleiotropic variants. To identify new pleiotropic variants and to determine whether loci identified in previous GWASs can also exert the same effect on lipid concentrations in Iranian population, longitudinal measurements of lipid variations were used in a sample of Iranian population (16,353 individuals within 3100 families) that followed up every 3 years and using a two-step model, the associations of 20,036 available SNPs on chromosome 16 were assessed. Twenty variants within the AC009035.1, SLC12A3, CETP, NLRC5, ESRP2 and, C16orf95 genes showed strong evidence for association with HDL-C, cholesterol, and triglycerides with p-values ranging from 1.7 × 10 Show less

The interaction of genetic and dietary factors, as an area of CVD research, has been explored poorly. The aim of the present study was to examine the interaction of dietary patterns and three genetic variants of APOA1 and APOC3, both independently and in combination, relative to the risk of the metabolic syndrome (MetS) in Tehranian adults. In the present matched, nested case-control study, 414 subjects with the MetS and 414 controls were selected from the participants of the Tehran Lipid and Glucose Study. Dietary patterns were determined by factor analysis. APOC3 (rs5128 3238C>G) and APOA1 (rs670, -75G>A and rs5069,+83C>T) SNP were genotyped by the conventional PCR followed by the restriction fragment length polymorphism technique. Overall, three major dietary patterns were extracted: healthy dietary pattern (HDP); Western dietary pattern (WDP); fat-sweet dietary pattern (FSDP). The A and T allele carriers of the APOA1 SNP had a greater risk of developing the MetS in the highest quartile of WDP scores (OR 3·22, 95 % CI 1·21, 8·58, P(interaction)= 0·03). Compared with other genotype combinations, the combined effect of APOC3/APOA1 (CC/GA+AA/CT+TT) genotypes showed a further increase in the risk of the MetS in the highest quartile of WDP scores (OR 1, 2·49, 8·73, 6·32, P trend< 0·001, P(interaction)= 0·003). A significant interaction was found between the quartiles of FSDP scores and the APOA1 diplotype (GA+AA/CT+TT). OR for these genotype carriers were 1, 0·65, 0·57 and 0·22 (P(trend)= 0·006) in the lowest to the highest quartile of FSDP scores when compared with the other combined genotypes (P(interaction)= 0·03). Our findings suggest that the WDP and FSDP are associated with APOA1 and APOC3 SNP in relation to the risk of the MetS. Show less

Gene-dietary pattern interactions may contribute to the determination of a susceptibility to metabolic syndrome (MetS). The aim of this study was to evaluate the potential interactions of dietary patterns with the common genetic variant of APOC3 in relation to MetS in adults. In this individual matched nested case-control study, 755 MetS subjects and 755 controls were selected from among participants in the Tehran Lipid and Glucose Study. Dietary patterns were determined by factor analysis. APOC3 3238C>G rs5128 was genotyped by polymerase chain reaction and restriction fragment length polymorphism. Fat-sweet, healthy and Western dietary patterns (WDP) were extracted from the data. In the joint analysis, the associations of the WDP and APOC3 rs5128 with MetS risk tended to be dependent on APOC3 3238C>G gene variants (p for interaction = 0.009) in women. The MetS risk was increased in women with the CC genotype with increasing tertiles of WDP scores compared with women with the CG + GG genotype, whose MetS risk was decreased with increasing tertiles of WDP scores. In addition, we found that intakes of fast food, salty snacks and soft drinks showed significant interactions with the rs5128 genotypes in relation to MetS risk (p for interactions <0.05). The results obtained demonstrate a diet-gene interaction between APOC3 rs5128 polymorphism and the WDP in relation to MetS risk. Show less

Logic regression is a generalized regression method that can recognize complex Boolean interactions of binary variables. It has been successfully applied to single-nucleotide polymorphism (SNP) data because of the importance of interactions in SNP association studies. The objective of this study is to assess the association between high-density lipoprotein (HDL) function and some related gene polymorphisms after adjusting for potential confounders using logic regression. Subjects in this cross-sectional study were randomly selected from among participants of the Tehran Lipid and Glucose Study (TLGS). A total of 436 subjects (172 men and 264 women), aged ≥20 years, were selected to be included in the current study. Logic regression analysis was used in order to recognize the combination of genetic main effects and possible interactions associated with HDL-C level. Cross validation and randomization test were carried out to avoid over fitting of the models. The cross validation test suggested three Boolean combinations with four predictors for a fully-adjusted logic model. The fully adjusted model showed that those who carry an Apo E gene E3 allele or have high TG level have an odds ratio of 2.35 (95% CI:1.3-4.25) for having low HDL compared to other subjects. In addition, subjects with high TG level have an odds ratio of 2.73 (95% CI: 1.65, 4.53) for having low HDL. The results showed that logic regression is a powerful method to find the interaction between high TG level and Apo E polymorphism associated with low HDL. Show less