PLA2G4A Research Articles

High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis

BackgroundIn mouse models of atherosclerosis, knockout of the PLA2G2A gene has been shown to reduce the volume of atherosclerotic plaques. Clinical trials have demonstrated the potential of using the sPLA2 inhibitor Varespladib in combination with statins to reduce lipid levels. However, this approach has not yielded the expected results in reducing the risk of cardiovascular events. Therefore, it is necessary to further investigate the mechanisms of PLA2G2A.MethodsSingle-cell transcriptome data from two sets of carotid plaques, combined with clinical patient information. were used to describe the expression characteristics of PLA2G2A in carotid plaques at different stages. In order to explore the mechanisms of PLA2G2A, we conducted enrichment analysis, cell–cell communication analysis and single-cell regulatory network inference and clustering analyses. We validated the above findings at the cellular level.ResultsOur findings indicate that PLA2G2A is primarily expressed in vascular fibroblasts and shows significant cell interactions with macrophages in the early-stage, especially in complement and inflammation-related pathways. We also found that serum sPLA2 levels have stronger diagnostic value in patients with mild carotid artery stenosis. Subsequent comparisons of single-cell transcriptomic data from early and late-stage carotid artery plaques corroborated these findings and predicted transcription factors that might regulate the progression of early carotid atherosclerosis (CA) and the expression of PLA2G2A.ConclusionsOur study discovered and validated that PLA2G2A is highly expressed by vascular fibroblasts and promotes plaque progression through the activation of macrophage complement and coagulation cascade pathways in the early-stage of CA.

STUB1-mediated K63-linked ubiquitination of UHRF1 promotes the progression of cholangiocarcinoma by maintaining DNA hypermethylation of PLA2G2A

BackgroundCholangiocarcinoma (CCA) is a highly malignant tumor characterized by a lack of effective targeted therapeutic strategies. The protein UHRF1 plays a pivotal role in the preservation of DNA methylation and works synergistically with DNMT1. Posttranscriptional modifications (PTMs), such as ubiquitination, play indispensable roles in facilitating this process. Nevertheless, the specific PTMs that regulate UHRF1 in CCA remain unidentified.MethodsWe confirmed the interaction between STUB1 and UHRF1 through mass spectrometry analysis. Furthermore, we investigated the underlying mechanisms of the STUB1-UHRF1/DNMT1 axis via co-IP experiments, denaturing IP ubiquitination experiments, nuclear‒cytoplasmic separation and immunofluorescence experiments. The downstream PLA2G2A gene, regulated by the STUB1-UHRF1/DNMT1 axis, was identified via RNA-seq. The negative regulatory mechanism of PLA2G2A was explored via bisulfite sequencing PCR (BSP) experiments to assess changes in promoter methylation. The roles of PLA2G2A and STUB1 in the proliferation, invasion, and migration of CCA cells were assessed using the CCK-8 assay, colony formation assay, Transwell assay, wound healing assay and xenograft mouse model. We evaluated the effects of STUB1/UHRF1 on cholangiocarcinoma by utilizing a primary CCA mouse model.ResultsThis study revealed that STUB1 interacts with UHRF1, resulting in an increase in the K63-linked ubiquitination of UHRF1. Consequently, this facilitates the nuclear translocation of UHRF1 and enhances its binding affinity with DNMT1. The STUB1-UHRF1/DNMT1 axis led to increased DNA methylation of the PLA2G2A promoter, subsequently repressing its expression. Increased STUB1 expression in CCA was inversely correlated with tumor progression and overall survival. Conversely, PLA2G2A functions as a tumor suppressor in CCA by inhibiting cell proliferation, invasion and migration.ConclusionsThese findings suggest that the STUB1-mediated ubiquitination of UHRF1 plays a pivotal role in tumor progression by epigenetically silencing PLA2G2A, underscoring the potential of STUB1 as both a prognostic biomarker and therapeutic target for CCA.Graphical

Inhibitory Effect and Mechanism of Epigallocatechin Gallate on the Differentiation of 3T3-L1 Preadipocytes.

Green tea possesses a range of beneficial effects, including anti-obesity, antioxidant, and anti-inflammatory properties, owing to its biologically active components, primarily catechins such as epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). However, few studies have investigated the four catechin monomers simultaneously, and the molecular mechanisms of their anti-obesity effects have not been fully elucidated. In this study, we investigated the effects of four catechin monomers on the differentiation of 3T3-L1 preadipocytes of mice. Our findings demonstrated that four catechin monomers EC/ECG/EGC/EGCG (12, 25, 50 µM) dose-dependently inhibited the differentiation of 3T3-L1 preadipocytes and reduced triglyceride content. EGCG exhibited the most potent inhibitory effect with an optimal concentration of 50 µM. In addition, transcriptome sequencing and lipidomic analysis of EGCG-treated 3T3-L1 preadipocytes revealed that Ptgs2 and Pim1 were the most differentially expressed genes involved in regulating adipocyte differentiation. The results suggested that EGCG up-regulated the expression of the Pla2g2e gene and down-regulated the expression of the Pla2g4a and Pla2g2a genes via the glycerophospholipid metabolic pathway, which subsequently elevated lysophosphatidylcholine (LPC) levels, influencing the differentiation process of 3T3-L1 preadipocytes.

Copy number deletion of PLA2G4A affects the susceptibility and clinical phenotypes of schizophrenia

Phospholipase A2(PLA2) superfamily is recognized as being involved in the pathogenesis of schizophrenia by affecting lipid homeostasis in cell membranes. We hypothesized that PLA2 gene copy number variation (CNV) may affect PLA2 enzyme expression and be associated with schizophrenia risk. This study indicated that in the discovery stage, an increased copy number of PLA2G6 and the deletion of PLA2G3, PLA2G4A, PLA2G4F and PLA2G12F was associated with increased risk of schizophrenia. CNV segments involving six PLA2 genes were detected in publicly available datasets, including two deletion segments specific to the PLA2G4A gene. The relationship between the deletion of PLA2G4A and susceptibility to schizophrenia was then reaffirmed in the validation group of 806 individuals. There was a significant correlation between PLA2G4A deletion and the symptoms of poverty of thought in male patients and erotomanic delusion in females. Furthermore, ELISA results demonstrate a significant decrease in peripheral blood cytosolic PLA2(cPLA2) levels in patients with the PLA2G4A deletion genotype compared to those with normal and copy number duplicate genotypes. These data suggest that the functional copy number deletion in the PLA2G4A gene is associated with the risk of schizophrenia and clinical phenotypes by reducing the expression of cPLA2, which may be an indicator of susceptibility to schizophrenia.

Identification of an Allele-Specific Transcription Factor Binding Interaction that May Regulate PLA2G2A Gene Expression.

The secreted phospholipase A2 (sPLA2) isoform, sPLA2-IIA, has been implicated in a variety of diseases and conditions, including bacteremia, cardiovascular disease, COVID-19, sepsis, adult respiratory distress syndrome, and certain cancers. Given its significant role in these conditions, understanding the regulatory mechanisms impacting its levels is crucial. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs), including rs11573156, that are associated with circulating levels of sPLA2-IIA. The work in the manuscript leveraged 4 publicly available datasets to investigate the mechanism by which rs11573156 influences sPLA2-IIA levels via bioinformatics and modeling analysis. Through genotype-tissue expression (GTEx), 234 expression quantitative trait loci (eQTLs) were identified for the gene that encodes for sPLA2-IIA, PLA2G2A. SNP2TFBS was used to ascertain the binding affinities between transcription factors (TFs) to both the reference and alternative alleles of identified eQTL SNPs. Subsequently, candidate TF-SNP interactions were cross-referenced with the ChIP-seq results in matched tissues from ENCODE. SP1-rs11573156 emerged as the significant TF-SNP pair in the liver. Further analysis revealed that the upregulation of PLA2G2A transcript levels through the rs11573156 variant was likely affected by tissue SP1 protein levels. Using an ordinary differential equation based on Michaelis-Menten kinetic assumptions, we modeled the dependence of PLA2G2A transcription on SP1 protein levels, incorporating the SNP influence. Collectively, our analysis strongly suggests that the difference in the binding dynamics of SP1 to different rs11573156 alleles may underlie the allele-specific PLA2G2A expression in different tissues, a mechanistic model that awaits future direct experimental validation. This mechanism likely contributes to the variation in circulating sPLA2-IIA protein levels in the human population, with implications for a wide range of human diseases.

Mutations of RAS genes identified in acute myeloid leukemia affect glycerophospholipid metabolism pathway.

Acute myeloid leukemia (AML) is a malignant disease originating from myeloid hematopoietic stem cells. Recent studies have shown that certain gene mutations promote tumor cell survival and affect the prognosis of patients by affecting metabolic mechanisms in tumor cells. RAS gene mutations are prevalent in AML, and the RAS signaling pathway is closely related to many metabolic pathways. However, the effects of different RAS gene mutations on AML cell metabolism are unclear. The main purpose of this study was to explore the effect of RAS gene mutation on the metabolic pathway of tumor cells. In this study, we first used a retrovirus carrying a mutant gene to prepare Ba/F3 cell lines with RAS gene mutations, and then compared full-transcriptome data of Ba/F3 cells before and after RAS gene mutation and found that differentially expressed genes after NRASQ61K and KRASG12V mutation. We found a total of 1899 differentially expressed genes after NRASQ61K and KRASG12V mutation. 1089 of these genes were involved in metabolic processes, of which 167 genes were enriched in metabolism-related pathways. In metabolism-related pathways, differential genes were associated with the lipid metabolism pathway. Moreover, by comparing groups, we found that the expression of the DGKzeta and PLA2G4A genes in the glycerophospholipid metabolism pathway was significantly upregulated. In conclusion, our study revealed that RAS gene mutation is closely related to the glycerophospholipid metabolism pathway in Ba/F3 cells, which may contribute to new precision therapy strategies and the development and application of new therapeutic drugs for AML.

Association between PLA2G4A and P2RX7 genes and eosinophilic phenotype and environment with pediatric asthma

Association between PLA2G4A and P2RX7 genes and eosinophilic phenotype and environment with pediatric asthma

Pla2g2a promotes innate Th2-type immunity lymphocytes to increase B1a cells

Newborns require early generation of effective innate immunity as a primary physiological mechanism for survival. The neonatal Lin28+Let7– developmental pathway allows increased generation of Th2-type cells and B1a (B-1 B) cells compared to adult cells and long-term maintenance of these initially generated innate cells. For initial B1a cell growth from the neonatal to adult stage, Th2-type IL-5 production from ILC2s and NKT2 cells is important to increase B1a cells. The Th17 increase is dependent on extracellular bacteria, and increased bacteria leads to lower Th2-type generation. Secreted group IIA-phospholipase A2 (sPLA2-IIA) from the Pla2g2a gene can bind to gram-positive bacteria and degrade bacterial membranes, controlling microbiota in the intestine. BALB/c mice are Pla2g2a+, and express high numbers of Th2-type cells and B1a cells. C57BL/6 mice are Pla2g2a-deficient and distinct from the SLAM family, and exhibit fewer NKT2 cells and fewer B1a cells from the neonatal to adult stage. We found that loss of Pla2g2a in the BALB/c background decreased IL-5 from Th2-type ILC2s and NKT2s but increased bacterial-reactive NKT17 cells and MAIT cells, and decreased the number of early-generated B1a cells and MZ B cells and the CD4/CD8 T cell ratio. Low IL-5 by decreased Th2-type cells in Pla2g2a loss led to low early-generated B1a cell growth from the neonatal to adult stage. In anti-thymocyte/Thy-1 autoreactive μκ transgenic (ATAμκ Tg) Pla2g2a+ BALB/c background C.B17 mice generated NKT2 cells that continuously control CD1d+ B1 B cells through old aging and lost CD1d in B1 B cells generating strong B1 ATA B cell leukemia/lymphoma. Pla2g2a-deficient ATAμκTg C57BL/6 mice suppressed the initial B1a cell increase, with low/negative spontaneous leukemia/lymphoma generation. These data confirmed that the presence of Pla2g2a to control bacteria is important to allow the neonatal to adult stage. Pla2g2a promotes innate Th2-type immunity lymphocytes to increase early generated B1a cells.

Tag-SNPs in Phospholipase-Related Genes Modify the Susceptibility to Nephrosclerosis and its Associated Cardiovascular Risk.

Nephrosclerosis patients have a high cardiovascular (CV) risk that is very often of more concern than the renal disease itself. We aimed to determine whether variants in phospholipase-related genes, associated with atherosclerosis and CV outcomes in the general population, could constitute biomarkers of nephrosclerosis and/or its associated CV risk. We screened 1,209 nephrosclerosis patients and controls for 86 tag-SNPs that were identified in the SCARB1, PLA2G4A, and PLA2G7 gene loci. Regression models were utilized to evaluate their effect on several clinical parameters. Most notably, rs10846744 and rs838880 in SCARB1 showed significant odds ratios (OR) of 0.66 (0.51–0.87), p = 0.003 and 1.48 (1.11–1.96), p = 0.007 for nephrosclerosis risk. PLA2G4A and PLA2G7 harboured several SNPs associated with atherosclerosis measurements in the patients, namely common carotid intima media thickness (ccIMT), presence of plaques, number of plaques detected and 2-years ccIMT progression (significant p-values ranging from 0.0004 to 0.047). Eight SNPs in PLA2G4A were independent risk factors for CV events in nephrosclerosis patients. Their addition to a ROC model containing classic risk factors significantly improved its predictive power from AUC = 69.1% (61.4–76.9) to AUC = 79.1% (73.1–85.1%), p = 0.047. Finally, PLA2G4A rs932476AA and rs6683619AA genotypes were associated with lower CV event-free survival after controlling for confounding variables [49.59 (47.97–51.21) vs. 51.81 (49.93–51.78) months, p = 0.041 and 46.46 (41.00–51.92) vs. 51.17 (50.25–52.08) months, p = 0.022, respectively]. Variability in phospholipase-related genes play a relevant role in nephrosclerosis and associated atherosclerosis measurements and CV events.

Dengue NS1 induces phospholipase A2 enzyme activity, prostaglandins, and inflammatory cytokines in monocytes

IntroductionDengue virus (DENV) NS1 is a non-structural secretory protein associated with severe disease and known to cause vascular leak leading to dengue haemorrhagic fever (DHF). As phospholipases A2 (PLA2) enzymes, platelet activating factor, and leukotrienes are elevated in dengue, we sought to investigate whether NS1 potentially contributes to disease pathogenesis by inducing PLA2s. MethodsTHP-1 cells and primary human monocytes of healthy adults (n = 6) were co-cultured with DENV1 NS1, LPS and media alone. The latter two were used as positive and negative controls. The cell culture supernatants and lysates were harvested at 12 and 24 h and the activity of secretory and cytoplasmic PLA2, prostaglandins (PGE2 and PGD2) were measured by ELISA and cytokines levels were measured using a magnetic Luminex assay. Expression of PLA2G4A, PLA2G2A, PLA2G5, PLA2G10, PLA2G7, GAPDH, NLRP3 and DDX58 genes were assessed using quantitative RT-PCR. ResultscPLA2 (p = 0.005), sPLA2 (p = 0.04), PGE2 metabolite (p = 0.02) and PGD2 metabolite (p = 0.04) levels were significantly higher at 12 h in monocytes co-cultured with NS1. Levels of IP-10 (p = 0.005) and IL-10 (p = 0.009) was significantly higher at 24 h, whereas IFNα level was significantly higher (p = 0.013) only at 12 h. IL-1β (p = 0.028 and p = 0.031) and TNFα (p = 0.007 and p = 0.011) showed significantly higher levels at both time points. At 12 h significant upregulation of PLA2G4A (p < 0.0001) was seen, whereas PLA2G7 (p = <0.0001), NLRP3 (p = 0.0009) and DDX58 (p = 0.0056) were significantly downregulated. This pattern changed at 24 h with PLA2G4A (p = 0.0069) showing a marked downregulation and PLA2G7, DDX58 and NLRP3 showing an upregulation, although not significant. ConclusionDengue NS1 induces the production of PLA2 enzymes, prostaglandins and inflammatory cytokines from primary human monocytes, which could play a role in vascular leak in dengue.

Cryptogenic multifocal ulcerating stenosing enteritis and other under-recognised small bowel inflammatory enteropathies.

Capsule endoscopy and more sensitive radiological techniques have resulted in more enteropathies being detected. A rare disease of unknown aetiology, 'cryptogenic multifocal ulcerating stenosing enteritis' or 'chronic nonspecific multiple ulcers of the small intestine' (CNSU), has long been recognised. This review aims to describe how disease can be better diagnosed and differentiated from other small bowel inflammatory disorders. Genetic studies have shown that some patients with CNSU (the term used in Japanese studies) express SLCO2A1 gene mutations, a gene which encodes a prostaglandin transporter expressed on vascular endothelium, allowing a more specific diagnosis of 'chronic enteropathy associated with SLCO2A1'. Mutations in the PLA2G4A gene result in cytosolic phospholipase A2α deficiency and reduced arachidonic acid for prostaglandin synthesis leading to a severe ulcerating, stenosing and fistulating small bowel disease. A 'prostaglandin-related enteropathy' should be considered in patients with atypical small bowel ulceration and stenosis. Genetic analysis will allow the detection of SLCO2A1 and PLA2G4A gene mutations. However, a careful history of medication use and a urinary metabolite screen may reveal the use of nonsteroidal anti-inflammatory drugs, a common cause of small bowel injury which is well recognised as being mediated by prostaglandin inhibition.

Therapeutic role of eicosapentaenoic and arachidonic acid in benzo(a) pyrene-induced toxicity in HUVEC endothelial cells

Endothelial cells are characterized by intense metabolic activity and control of homeostasis. Exposure to benzo(a)pyrene (BaP) plays an important role in the etiology of atherosclerosis. The study aimed to determine the effect of arachidonic (ARA), and eicosapentaenoic acid (EPA) on pro-inflammatory gene and protein levels in human umbilical vein endothelial cells (HUVEC) exposed to BaP. Cyclooxygenase-2 (COX-2), aryl hydrocarbon receptor (AHR), and glutathione S transferase Mu1 (GSTM1) proteins expression were analyzed by Western blot. Prostaglandin synthase 2 (PTGS2), AHR, GSTM1, phospholipase A2 (PLA2G4A), cytochrome P450 CYP1A1, intercellular adhesion molecule-1 (ICAM-1), endothelial nitric-oxide synthase (NOS3), and vascular adhesion molecule-1 gene expression (VCAM-1) was analyzed in Real time-qPCR. Phospholipase A2 activity was measured using the ELISA technique, and CYP1A1 activity was analyzed in luminescence assay.The highest amount of COX-2, the most increased activity of CYP1A1 and cPLA2, and overexpression of GSTM1, CYP1A1, ICAM-1, and VCAM-1 gene was observed in HUVEC cells treated with BaP. After co-treatment with BaP and ARA or EPA, an increase of GSTM1 level was observed. Incubation of endothelial cells with ARA or EPA and BaP resulted in lower CYP1A1 and cPLA2 activities and lower expression of VCAM-1 and ICAM-1 genes. Significant overexpression of AHR, GSTM1, CYP1A1, PTGS2, PLA2G4A, and NOS3 genes was noted in cells treated with EPA and BaP.Our data suggest a beneficial effect of EPA and ARA on endothelial function. Thus, it justifies further research on the participation of fatty acids in the regulation of physiological and pathological processes in endothelial cells.

Effect of copy number variation of PLA2G2A gene to growth traits in Chinese cattle.

As a member of genetic polymorphism, copy number variation has been a commonly used method in the world for investigating effect of genetic polymorphism on gene expression. Effect of genetic polymorphism made on livestock development has been more and more important in beef cattle molecular breeding. The characteristics of Chinese cattle are excellent meat quality, tolerant to rough feeding, good environmental adaptability and so on. But there are some obvious weaknesses still exist in the process of cattle growth and development, such as weak hindquarters and growth slowly. To improve the growth performance and market competitiveness of Chinese cattle, a lot of studies have been made about finding and investigating effective molecular marker. In this study, Q-PCR and data association analysis were used for PLA2G2A gene copy number variation detection and related effect analysis in Chinese cattle. Results showed that PLA2G2A gene has a significant effect on two breeds of Chinese cattle on growth traits, which could be a basic materials and effective information of cattle molecular markers breeding. PLA2G2A, member of secreted phospholipases A2 (sPLA2) in superfamily of phospholipase A2, could catalyze the process of glycerophospholipids hydrolysis from position of sn-2 acyl with the release of free fatty acids and lysophospholipids. Researches about PLA2G2A gene are mostly focus on disease, including tumors and diabetes, the number of study occurred on animal breeding is weak. In this study, blood samples were collected from five breeds of Chinese cattle (Qingchuan cattle, Xianan cattle, Yunling cattle, Pinan cattle and Guyuan cattle) for PLA2G2A gene CNV type detection. SPSS 20.0 software and method of ANOVA were used to analyzed the association between types of CNV and growth traits. Results reveal that the distribution of different copy number types in different cattle breeds is different. In QC, XN and GY cattle, the frequencies of Deletion and Duplication are about 40%; in YL cattle, the frequency of Deletion type exceeds 60%; in PN cattle, the frequency of Duplication is closed to 80%. Association analysis indicate that CNV of PLA2G2A gene showed a positive effect in cattle growth: in QC cattle, Chest depth with Normal type copy number possess a increased trend (P<0.05); individuals with Deletion type copy number have better performance on Height at sacrum, Heart girth and Body height in GY cattle (P<0.05). The functional role and molecular mechanism of PLA2G2A gene in animal growth and development are still unclear, and it is necessary for processing a further research. This research aims to provide basic materials for molecular breeding of Chinese cattle.

Effect of Eicosapentaenoic Acid Supplementation on Murine Preadipocytes 3T3-L1 Cells Activated with Lipopolysaccharide and/or Tumor Necrosis Factor-α.

The beneficial effect of n-3 fatty acids can be related to anti-inflammatory properties. The aim of the study was to analyzed the effect of eicosapentaenoic acid (EPA) on 3T3-L1 cells (murine embryonic fibroblasts‒preadipocytes) activated with inflammatory factors (IF). Cells were incubated with 50 µmol of EPA for 48 h, and then activated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The level of cycloxygenase-2 (Prostaglandin-Endoperoxide Synthase 2, PTGS2, COX-2), cytosolic prostaglandin synthase E2 (cPGES), fatty acid binding protein 4 (FABP4), toll-like receptor 4 (TLR4), glucose receptor type 4 (GLUT-4), and cannabinoid receptor 2 (CB2) was determined using Western blot analysis. The phospholipase A2 (Pla2g4a), and prostaglandin-Endoperoxide Synthase 2 (Ptgs2) gene expression was analyzed by real-time qPCR. After EPA and IF activation, a significant decrease in the COX-2, cPGES, and TRL4 protein levels was observed. Incubation of cells with EPA and IF resulted in a decrease in Ptgs2 and an increase in the Pla2g4a gene. A significant increase in the CB2 protein was observed in adipocytes co-treated with EPA and IF. The results indicated an anti-inflammatory properties of EPA. Interestingly, the activation of the GLUT4 receptor by EPA suggests an unique role of this FA in the regulation of the adipocyte metabolism and prevention of insulin resistance.

Genetic Diversity and Identification of Homozygosity-Rich Genomic Regions in Seven Italian Heritage Turkey (Meleagris gallopavo) Breeds.

Italian autochthonous turkey breeds are an important reservoir of genetic biodiversity that should be maintained with an in vivo approach. The aim of this study, part of the TuBAvI national project on biodiversity, was to use run of homozygosity (ROH), together with others statistical approaches (e.g., Wright’s F-statistics, principal component analysis, ADMIXTURE analysis), to investigate the genomic diversity in several heritage turkey breeds. We performed a genome-wide characterization of ROH-rich regions in seven autochthonous turkey breeds, i.e., Brianzolo (Brzl), Bronzato Comune Italiano (BrCI), Bronzato dei Colli Euganei (CoEu), Parma e Piacenza (PrPc), Nero d’Italia (NeIt), Ermellinato di Rovigo (ErRo) and Romagnolo (Roma). ROHs were detected based on a 650K SNP genotyping. ROH_islands were identified as homozygous ROH regions shared by at least 75% of birds (within breed). Annotation of genes was performed with DAVID. The admixture analyses revealed that six breeds are unique populations while the Roma breed consists in an admixture of founder populations. Effective population size estimated on genomic data shows a numeric contraction. ROH_islands harbour genes that may be interesting for target selection in commercial populations also. Among them the PTGS2 and PLA2G4A genes on chr10 were related to reproduction efficiency. This is the first study mapping genetic variation in autochthonous turkey populations. Breeds were genetically different among them, with the Roma breed proving to be a mixture of the other breeds. The ROH_islands identified harboured genes peculiar to the selection that occurred in heritage breeds. Finally, this study releases previously undisclosed information on existing genetic variation in the turkey species.

Association of 5'UTR polymorphism of secretory phospholipase A2 group IIA (PLA2G2A) gene with prostate cancer metastasis.

Phospholipase A2 (PLA2) enzymes are small lipolytic hydrolases that can regulate immune responses through generation of Arachidonic Acid (AA), a precursor molecule of lipid mediators like prostaglandins, leukotrienes and thromboxanes. One of the family members of PLA2, secretory Phospholipase A2 Group IIA (PLA2G2A), was associated with different types of malignancies including prostate cancer. Elevated serum levels of PLA2G2A was found in prostate cancer (PCa) patients and associated with increased tumor grade in literature. 5'UTR regions have regulatory role in protein expression by controlling the accessibility of factors necessary for the translation initiation. Single nucleotide polymorphisms at 5'UTR regions have the potential to affect mRNA translation efficiency resulting in altered protein levels depending on structure and nucleotide content. Given that the 5'UTR polymorphism in PLA2G2A gene (rs11573156) is associated with increased serum levels of PLA2G2A, the association of this 5'UTR polymorphism with PCa susceptibility and metastasis was investigated in this study. Total of 261 PCa patients and 128 control individuals were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Individuals with heterozygous CG genotype was found to have significantly reduced risk of PCa metastasis with an Odds Ratio (OR) of 0.405 (p=0.028, 95%CI=0.181-0.906), compared to the carriers of homozygous CC genotype (p>0.05) suggesting an anti-metastatic effect for the G allele. No association was found between PCa susceptibility and Gleason score (p>0.05) in Turkish population.

Polymorphism of Secretary PLA2G2A Gene Associated with Its Serum Level in Type2 Diabetes Mellitus Patients in Northern Iran

Inflammation may occur in Type2 diabetes mellitus. sPLA2 is among the factors that contribute to the activation of pathways involved in inflammation. Several agents affect serum sPLA2 level, one of which is genetic diversity. The current study was performed to determine whether there is a relationship between sPLA2 gene (-763C > G) polymorphism and circulating sPLA2 level in patients with Type 2 diabetes. DNA was extracted from blood samples and used for the amplification of sPLA2 gene using ARMS-PCR. A statistical analysis using SPSS (version 16) revealed a significant correlation between -763C > G sPLA2 gene polymorphisms and the disease incidence in patients with T2DM. Among the three possible genotypes (GG, CC, and CG), CG genotype was found to have a higher frequency(53%) in T2DM patients. GG and CC genotypes frequencies were 20 and 27%, respectively. In healthy individuals, the frequencies of CC, GG, and GC genotypes were 77, 9.8% and 13.2%, respectively). Patients with genotype GG had the highest level of sPLA2. We showed that C>G polymorphism at position- 763 is associated with a high level of sPLA2 in both T2DM patients and healthy individuals. The average of sPLA2 circulating level was (170.48± 84.90), (106.62 ± 74.31), in patients and normal individuals, respectively. Our findings show that sPLA2 serum level is significantly higher in patients with T2DM disease than that in healthy individuals.

Supplementation with omega fatty acids increases the mRNA expression level of PLA2G4A in patients with gastric cancer.

Many lines of evidence suggest that arachidonic acid (AA)-based eicosanoid signaling pathway involved in development and progression of human cancers. Cytosolic phospholipase A2-α (cPLA2α) encoded by the PLA2G4A gene acts as an upstream regulator of eicosanoid signaling pathway through providing intracellular AA. The current study aimed to evaluate the effect of omega fatty acids on mRNA expression level of PLA2G4A in patients with gastric cancer (GC) and to assess the possible relation between its expression and clinicopathological features. According to treatment strategy, 34 chemotherapy-naive patients were randomly divided into two groups including, treatment group I (17 subjects received cisplatin alone) and treatment group II (17 individuals received cisplatin plus omega fatty acids) in a double-blind manner. The gastric biopsies specimens were taken from subjects before and after treatment and then mRNA expression level of PLA2G4A was evaluated by quantitative real-time PCR procedure. The expression of the PLA2G4A gene at the protein level in the gastric biopsies samples was also determined by immunohistochemistry. Our findings revealed a significantly up-regulated expression of PLA2G4A mRNA in treatment group II after receiving cisplatin plus omega fatty acid compared to before treatment (P=0.003). In treatment group I, there was no significant difference in mRNA expression levels of PLA2G4A before and after treatment (P=0.790). We also found that mRNA expression of PLA2G4A in treatment group II was significantly associated with tumor size (P=0.007) and familial history (P=0.006). This study provides evidence that supplementation with omega fatty acids increases the mRNA expression level of PLA2G4A in patients with GC and may be crucial in guarding the cell from transformation and carcinogenesis.

Genetic analysis is helpful for the diagnosis of small bowel ulceration.

The widespread use of capsule endoscopy and balloon-assisted endoscopy has provided easy access for detailed mucosal assessment of the small intestine. However, the diagnosis of rare small bowel diseases, such as cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), remains difficult because clinical and morphological features of these diseases are obscure even for gastroenterologists. In an issue of this journal in 2017, Hwang et al reviewed and summarized clinical and radiographic features of 20 patients with an established diagnosis of CMUSE. Recently, recessive mutations in the PLA2G4A and SLCO2A1 genes have been shown to cause small intestinal diseases. The small bowel ulcers in each disease mimic those in the other and furthermore those found in nonsteroidal anti-inflammatory drug-induced enteropathy. These recent and novel findings suggest that a clinical diagnosis exclusively based on the characteristics of small bowel lesions is possibly imprecise. Genetic analyses seem to be inevitable for the diagnosis of rare small bowel disorders such as CMUSE.

An association between the BanI polymorphism of the PLA2G4A gene for calcium-dependent phospholipase A2 and plasma glucose levels among females with schizophrenia

Abnormal glucose and lipid metabolism may be associated with altered cytosolic Ca2+-dependent phospholipase A2 (cPLA2) signaling in patients with schizophrenia. The relationship between schizophrenia and the functional BanI polymorphism (rs10798059 variant, A/G polymorphism) of the PLA2G4A gene for cPLA2 has been extensively investigated. We previously reported that it can influence several clinical features of schizophrenia, and it was shown to contribute to schizophrenia risk in several population studies. We performed PCR/RFLP genotyping of 263 Croatian patients (males/females: 139/124) to investigate the relationship between the BanI polymorphism and fasting plasma glucose and lipid levels in patients with schizophrenia. Our results indicate that the BanI polymorphic variant contributes significantly to plasma glucose levels in female patients. Females carrying the PLA2G4A-G allele (PLA2G4A-GG homozygous and PLA2G4A-AG heterozygous) presented with lower glucose levels than PLA2G4A-AA homozygous carriers, and the PLA2G4A genotype contributed approximately 6% of plasma glucose level variability in this group of patients.