scholarly journals Impact of Proliferator-Activated Receptor γ Gene Polymorphisms on Risk of Schizophrenia: A Case-Control Study and Computational Analyses

2020 ◽  
Author(s):  
Saman Sargazi ◽  
Fariba Mirani Sargazi ◽  
Mahdiyeh Moudi ◽  
Milad Heidari Nia ◽  
Ramin Saravani ◽  
...  
Keyword(s):  
Protein Function ◽  
Amplification Refractory Mutation System ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Replication Studies ◽  
Codominant Model ◽  
Mutation System ◽  
Pparg Gene ◽  
Computational Analyses ◽  
Relationship Of

Objective: Schizophrenia (SCZ) is a common psychiatric disorder characterized by a complex mode of inheritance. Peroxisome proliferator-activated receptor-γ (PPARG) mainly regulates lipid and glucose metabolisms while it is constitutively expressed in rat primary microglial cultures. This preliminary study was aimed to investigate the relationship of two polymorphisms in the PPARG gene, rs1801282 C/G, and rs3856806 C/T, to the risk of SCZ in the southeast Iranian population. Method: A total of 300 participants (150 patients with SCZ and 150 healthy controls) were enrolled. Genotyping was done using the amplification refractory mutation system polymerase chain reaction (ARMS–PCR) technique. Computational analyses were carried out to predict the potential effects of the studied polymorphisms. Results: A significant link was found between genotypes of rs1801282 and SCZ susceptibility. The G allele of rs1801282 in CG and GG form of the codominant model increased the risk of SCZ by 2.49 and 2.64 folds, respectively. With regards to rs3856806, enhanced risk of SCZ was also observed under different inheritance models except for the overdominant model. Also, the T allele of rs3856806 enhanced the risk of SCZ by 3.19 fold. Computational analyses predicted that rs1801282 polymorphism might alter the secondary structure of PPARG-mRNA and protein function. At the same time, the other variant created the binding sites for some enhancer and silencer motifs. Conclusion: Our findings showed that PPARG rs1821282 and rs3856806 polymorphisms associate with SCZ susceptibility. Replication studies in different ethnicities with a larger population are needed to validate our findings.  

scholarly journals Effects of the PPARG Gene Polymorphisms on Markers of Obesity and the Metabolic Syndrome in Bosnian Subjects

2014 ◽  
Vol 33 (4) ◽  
pp. 323-332 ◽  
Author(s):  
Tanja Dujić ◽  
Tamer Bego ◽  
Barbara Mlinar ◽  
Sabina Semiz ◽  
Maja Malenica ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Metabolic Phenotype ◽  
Polymorphism Analysis ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Metabolic Syndrome ◽  
Obesity And Diabetes ◽  
Pparg Gene ◽  
Relationship Of

Summary Background: Peroxisome proliferator-activated receptor gamma (PPARg) is a key transcription factor in adipogene-sis, and also regulates a number of genes associated with lipid storage and insulin sensitivity. Single nucleotide polymorphisms (SNPs) in the PPARG gene have been associated with obesity and diabetes. In this study, we explored the relationship of three PPARG gene variants with the metabolic syndrome (MetS) and related traits in a population from Bosnia and Herzegovina. Methods: Anthropometric and biochemical parameters were measured in 43 patients with MetS and 43 healthy controls. Subjects were genotyped for Pro12Ala (rs1801282) and 1431C>T (rs3856806) SNPs by classic PCR–restriction fragment length polymorphism analysis, and for-681C>G (rs10865710) variant by real-time PCR. Results: The genotype distributions for the three polymorphisms were not significantly different between MetS patients and controls. The Pro12Ala and 1431C>T variants were associated with lower body mass index in the control subjects (p=0.012 and p=0.049, respectively). In this group, the carriers of Pro12Ala had also lower waist circumference compared to the wild-type homozygotes (p=0.045). Conclusions: Results of our preliminary study indicate a beneficial effect of a common Pro12Ala variant on the metabolic phenotype in healthy non-obese subjects.

MirSNPs in clopidogrel metabolism genes predict cardiovascular disease risk: a case–control study and meta-analysis

2020 ◽  
Author(s):  
Anu Radha Sharma ◽  
Sourav Patagi ◽  
Abdul Razak UK ◽  
Ranjan Shetty ◽  
Shashikiran Umakanth ◽  
...  
Keyword(s):  
Case Control Study ◽  
Disease Risk ◽  
Meta Analysis ◽  
Cardiovascular Disease Risk ◽  
Case Control ◽  
Amplification Refractory Mutation System ◽  
Mutation System ◽  
Artery Disease ◽  
Relationship Of ◽  
Control Study

Aim: The present study was conducted to decipher the inter-relationship of SNPs and miRNAs involved in pharmacogenomics of clopidogrel on predisposition to cardiovascular diseases (CVDs). Materials & methods: A case–control study was conducted on 410 cases and 386 controls to analyze the association of 13 mirSNPs on CVDs risk. Genotyping was performed by tetra-primer amplification refractory mutation system PCR and validated using Sanger DNA sequencing. miRNA expression analysis was performed using TaqMan assays. A meta-analysis was performed for PON1 rs662 with coronary artery disease. Results & conclusion: PON1 rs662, PON1 rs3917577, CYP3A5 rs15524, COL4A1 rs874204 and PTGIR rs1126510 polymorphisms showed association with CVDs. The miRNA hsa-miR-224-5p showed differential expression in the PON1 rs3917577 GG genotype. The meta-analysis showed the population-specific impact of PON1 rs662 on South Asian and Middle East populations.

STUDI IN SILICO DAN HUBUNGAN KUANTITATIF STRUKTUR TERHADAP AKTIVITAS TANAMAN MANGROVE (Avicennia marina (Forssk.) Vierh.) SEBAGAI ANTIDIABETES

2020 ◽  
Vol 2 (1) ◽  
pp. 112
Author(s):  
Arinil Hidayati ◽  
Siswandono Siswandono ◽  
Pramudita Riwanti
Keyword(s):  
Regression Analysis ◽  
In Silico ◽  
Avicennia Marina ◽  
Three Dimensions ◽  
Peroxisome Proliferator ◽  
Nonlinear Relationship ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molegro Virtual Docker ◽  
Relationship Of

The research is applied to 20 compounds contained  into <em>Avicennia marina</em> which is : <em>4’,5-dihydroxy-3’,5’,7-trimethoxyflavone, isorhamnetin 3-O-rutinoside, quercetin, stenocarproquinone B, avicennone C, avicennone E, avicennone F, avicennone D,   4’,5-dihydroxy-3’,7-dimethoxyflavone, chrysoeriol 7-O-glucoside, naphta(1,2-b)furan-4,5-dione, 3-hydroxy-naphta(1,2-b)furan-4,5-dione, kaempferol, 5-hydroxy-4’,7-dimethoxyflavone, avicequinone C, 2-[2’-(2’-hydroxy)propyl]-naphta[1,2-b]furan-4,5-dione, 4’,5,7-trihydroxyflavone, luteolin 7-O-methylether, luteolin 7-O-methylether 3’-O-beta-D-glucoside, 5,7-dihydroxy-3’,4’,5’-trimethoxyflavone</em> which are expected  to have an  effect as antidiabetics agent. It is undertaken to find out the linier or nonlinier relationship of  the structure activty (QSAR), the physicochemical characters (lipophilic, electronic, dan steric) to the activity changing (<em>rerank score</em>). Moreover, it is also undertaken to find out which one of those 20 <em>Avicennia marina </em>compounds are predicted to possess the activity as the best antidiabetics agent by the comparison of pioglitazon. It is arranged through computerized methods or <em>in silico</em> not only for having  the structure of two and three dimensions but also knowing the physicochemical characters too; through some programs such as  <em>ChemBioDraw Ultra </em>12.0 and <em>ChemBio3D Ultra </em>12.0 from <em>CambridgeSoft. The docking </em>program is used to make prediction of  the activity  by using <em>Molegro Virtual  Docker </em>2011.5.0.0 from CLCBio<em>.</em> by using the <em>peroxisome proliferator-activated receptor-gamma </em>(PPAR𝛾) in code of PDB: 2XKW. The result of the regression analysis through IBM SPSS program shows nonlinear relationship among structures, <em>Avicennia marina</em> physicochemical characters of twenty compound contents dealing with the activity changing. The compound of  <em>isorhamnetin 3-O-rutinoside</em><em>, chrysoeriol 7-O-glucoside, </em>and <em>luteolin 7-O-methylether 3’-O-beta-D-glucoside </em>are predicted to have the best antidiabetics agent if it is compared with the comparing drug pioglitazon.

Probing the effect of MODY mutations near the co-activator-binding pocket of HNF4α

2011 ◽  
Vol 31 (5) ◽  
pp. 411-419 ◽  
Author(s):  
Geun Bae Rha ◽  
Guangteng Wu ◽  
Young-In Chi
Keyword(s):  
Protein Function ◽  
Structural Integrity ◽  
Cell Function ◽  
Point Mutations ◽  
Binding Pocket ◽  
Peroxisome Proliferator ◽  
Loss Of Function ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ligand Selectivity ◽  
Β Cell Function

HNF4α (hepatocyte nuclear factor 4α) is a culprit gene product for a monogenic and dominantly inherited form of diabetes, referred to as MODY (maturity onset diabetes of the young). As a member of the NR (nuclear receptor) superfamily, HNF4α recruits transcriptional co-activators such as SRC-1α (steroid receptor co-activator-1α) and PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) through the LXXLL-binding motifs for its transactivation, and our recent crystal structures of the complex provided the molecular details and the mechanistic insights into these co-activator recruitments. Several mutations have been identified from the MODY patients and, among these, point mutations can be very instructive site-specific measures of protein function and structure. Thus, in the present study, we probed the functional effects of the two MODY point mutations (D206Y and M364R) found directly near the LXXLL motif-binding site by conducting a series of experiments on their structural integrity and specific functional roles such as overall transcription, ligand selectivity, target gene recognition and co-activator recruitment. While the D206Y mutation has a subtle effect, the M364R mutation significantly impaired the overall transactivation by HNF4α. These functional disruptions are mainly due to their reduced ability to recruit co-activators and lowered protein stability (only with M364R mutation), while their DNA-binding activities and ligand selectivities are preserved. These results confirmed our structural predictions and proved that MODY mutations are loss-of-function mutations leading to impaired β-cell function. These findings should help target selective residues for correcting mutational defects or modulating the overall activity of HNF4α as a means of therapeutic intervention.

scholarly journals The role of A268V exon-7 polymorphism of PPARA in development of axial spondyloarthritis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ekrem Akbulut ◽  
Servet Yolbas ◽  
Metin Ozgen
Keyword(s):  
Ligand Binding ◽  
Axial Spondyloarthritis ◽  
Disease Risk ◽  
Axial Skeleton ◽  
Chronic Inflammatory Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Docking Program ◽  
Relationship Of

Abstract Objectives Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton. Peroxisome proliferator activated receptor alpha (PPARA) is an intracellular transcription factor, which play a role in inflammation and osteoblasting activity. This study is designed to investigate the relationship of NG_012204.2:p.Ala268Val polymorphism of PPARA with axSpA risk and its role in disease development. Methods This study was conducted with 168 patients and 181 controls. Genotyping was done with MALDITOF. Gene expression level was analyzed by quantitative real time PCR (RT-qPCR). The protein homology models of PPARA were created with ProMod3. Ligand binding dynamics were tested using the AutoDock4 docking program. Statistical evaluations were made with SPSS (ver24) and GeneGlobe. Results Our results showed that C>T polymorphism causing NG_012204.2:p.Ala268Val change was associated with disease risk (p=0.024) and T allele increased disease risk 1.7 times (95% CI=1.070–2.594). PPARA expression decreased (p<0.05) in individuals carrying the T allele. We determined that the ligand entry pocket was opened 1.1 Å in the polymorphic PPARA. Polymorphic change caused a decrease in the ligand binding affinity. Conclusions Our results provide an important contribution to elucidating the development of axSpA and demonstrate the potential of PPARA as a marker for the diagnosis of axSpA.

scholarly journals Post-Treatment with Amorfrutin B Evokes PPARγ-Mediated Neuroprotection against Hypoxia and Ischemia

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 854
Author(s):  
Agnieszka Wnuk ◽  
Karolina Przepiórska ◽  
Bernadeta A. Pietrzak ◽  
Małgorzata Kajta
Keyword(s):  
Protein Expression ◽  
Neuroprotective Effect ◽  
Primary Cultures ◽  
Post Treatment ◽  
Receptor Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Pparg Gene

In this study, we demonstrate for the first time that amorfrutin B, a selective modulator of peroxisome proliferator-activated receptor gamma—PPARγ, can protect brain neurons from hypoxia- and ischemia-induced degeneration when applied at 6 h post-treatment in primary cultures. The neuroprotective effect of amorfrutin B suggests that it promotes mitochondrial integrity and is capable of inhibiting reactive oxygen species—ROS activity and ROS-mediated DNA damage. PPARγ antagonist and Pparg mRNA silencing abolished the neuroprotective effect of amorfrutin B, which points to agonistic action of the compound on the respective receptor. Interestingly, amorfrutin B stimulated the methylation of the Pparg gene, both during hypoxia and ischemia. Amorfrutin B also increased the protein level of PPARγ during hypoxia but decreased the mRNA and protein levels of PPARγ during ischemia. Under ischemic conditions, amorfrutin B-evoked hypermethylation of the Pparg gene is in line with the decrease in the mRNA and protein expression of PPARγ. However, under hypoxic conditions, amorfrutin B-dependent hypermethylation of the Pparg gene does not explain the amorfrutin B-dependent increase in receptor protein expression, which suggests other regulatory mechanisms. Other epigenetic parameters, such as HAT and/or sirtuins activities, were affected by amorfrutin B under hypoxic and ischemic conditions. These properties position the compound among the most promising anti-stroke and wide-window therapeutics.

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