Paraoxonase gene polymorphisms and haplotype analysis in a stroke population

Peer reviewedPublisher PD

Un nuevo antioxidante: 6,6'-(butano-1,1-diil)bis(4-metil-benceno-1,2-diol)

A novel compound, 6,6'-(butane-1,1-diyl)bis(4-methylbenzene-1,2-diol) (BMB), was synthesized through an acid-catalyzed condensation reaction between 4-methylcatechol (HPC) and butyraldehyde. When evaluated by the Rancimat and deep frying methods, BMB exhibited a stronger antioxidant activity than TBHQ. Its DPPH radical scavenging activity was also fairly higher than TBHQ, but lower compared to its mother phenol, HPC, due to its relative ease of binding DPPH•. BMB had the strongest scavenging ability of the 4-methylcatechol analogues reported to date. It could be used effectively to retard lipid peroxidation in both moderate and high temperature food preparations.Un nuevo compuesto, 6,6'-(butano-1,1-diil)bis(4-metilbenceno-1,2-diol) (BMB) fue sintetizado mediante una reacción de condensación catalizada por ácido entre el 4-metilcatecol (HPC) y el butiraldehído. Cuando se evaluó mediante los métodos Rancimat y de fritura, el BMB mostró una actividad antioxidante más fuerte que el TBHQ. Su actividad de eliminación de radicales DPPH también fue bastante mayor que la del TBHQ, pero menor en comparación con el fenol de partida, HPC, debido a su relativa facilidad para unirse a DPPH•. BMB tiene una actividad de eliminación más fuerte que los análogos de 4-metilcatecol reportados hasta la fecha. Podría usarse eficazmente para retardar la peroxidación de lípidos en la preparación de alimentos a temperatura moderada y alta

Synthesis, structural characterization and biological activity of Cu(II), Co(II) and Ni(II) complexes derived from 2-(thiazol-2-ylimino)thiazolidin-4-one ligand

A novel series of metal complexes of 2-(thiazol-2-ylimino) thiazolidin-4-one ligand were prepared; the corresponding ligand was synthesized from reaction 2-Chloro-N-(thiazol-2-yl) acetamide with ammonium thiocyanate. The complexes are characterized by FTIR, UV-Vis, molar conductance and mass spectroscopy. The low molar conductance values indicate that the complexes are non-electrolytes.Spectroscopic studies confirmed that the ligand bonded to the metals through the sulphur atoms. Coordination number of copper and nickel complexes is four with square planar geometry, while the cobalt complex has octahedral geometry.In vitro antibacterial activity of ligand and its metal complexes was evaluated using well diffusion method and compared to the standard drug (tetracycline). The antibacterial activitywas examined against Escherichia coli, and pseudomonas aeruginosa, as gram negative bacteria and Staphylococcus aureus as gram positive bacteria. It was found that Nickel complex has the highest antibacterial activity among the synthesized compounds with Zone inhibition diameter in the range 25-29 mm

Using of Naproxen drug for novel synthesis of 4-thiazolidinone derivatives and application of these drugs as no steroidal anti-inflammatory drug (NSAIDs) and as anti-epileptic agent

Non-steroidal anti-inflammatory drugs (NSAIDs) are now one of the most frequent drugs used in treatment of pain, inflammation and fever. In this study the aim is the synthesis of derivatives of 4-Tiazolidinon from naproxen with the possible anti-pain effects, and the main purpose of providing these derivatives is to achieve a compound with more anti-pain power and less side effects in comparison with applied drugs in clinics. Synthesis of these derivatives is done on chloride in presence of a group of new liquids like recyclable ionic liquids choline chloride, which the main advantages of these ionic liquids are the cheapness, availability, being non-toxic, and easy recyclability. This reaction was done in four stages. All the structures were verified by using data of spectrum testing, 1H-NMR, FT-IR

Association of RS4784227-casc16 (Loc643714 locus) and RS4782447-ACSF3 polymorphisms and their association with breast cancer risk among iranian population

Peer reviewedPublisher PD

AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data.

Homozygosity mapping is a powerful method for identifying mutations in patients with recessive conditions, especially in consanguineous families or isolated populations. Historically, it has been used in conjunction with genotypes from highly polymorphic markers, such as DNA microsatellites or common SNPs. Traditional software performs rather poorly with data from Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS), which are now extensively used in medical genetics. We develop AutoMap, a tool that is both web-based or downloadable, to allow performing homozygosity mapping directly on VCF (Variant Call Format) calls from WES or WGS projects. Following a training step on WES data from 26 consanguineous families and a validation procedure on a matched cohort, our method shows higher overall performances when compared with eight existing tools. Most importantly, when tested on real cases with negative molecular diagnosis from an internal set, AutoMap detects three gene-disease and multiple variant-disease associations that were previously unrecognized, projecting clear benefits for both molecular diagnosis and research activities in medical genetics

Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration

BACKGROUND & AIMS: Excess liver iron content is common and is linked to hepatic and extrahepatic disease risk. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. METHODS: First, we performed a genome-wide association study (GWAS) in 8,289 individuals in UK Biobank with MRI quantified liver iron, and validated our findings in an independent cohort (n=1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 29 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 anthropometric traits and diseases. RESULTS: We identified three independent genetic variants (rs1800562 (C282Y) and rs1799945 (H63D) in HFE and rs855791 (V736A) in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p < 5x10-8). The two HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. CONCLUSION: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. LAY SUMMARY: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We find that three genetic variants are linked to increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content

A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes

Obesity and type 2 diabetes are causally related, yet there is considerable heterogeneity in the consequences of both conditions and the mechanisms of action are poorly defined. Here we show a genetic-driven approach defining two obesity profiles that convey highly concordant and discordant diabetogenic effects. We annotate and then compare association signals for these profiles across clinical and molecular phenotypic layers. Key differences are identified in a wide range of traits, including cardiovascular mortality, fat distribution, liver metabolism, blood pressure, specific lipid fractions and blood levels of proteins involved in extracellular matrix remodelling. We find marginal differences in abundance of Bacteroidetes and Firmicutes bacteria in the gut. Instrumental analyses reveal prominent causal roles for waist-to-hip ratio, blood pressure and cholesterol content of high-density lipoprotein particles in the development of diabetes in obesity. We prioritize 17 genes from the discordant signature that convey protection against type 2 diabetes in obesity, which may represent logical targets for precision medicine approaches.</p

The effect of ABCA1 gene polymorphisms on ischaemic stroke risk and relationship with lipid profile

<p>Abstract</p> <p>Background</p> <p>Ischaemic stroke is a common disorder with genetic and environmental components contributing to overall risk. Atherothromboembolic abnormalities, which play a crucial role in the pathogenesis of ischaemic stroke, are often the end result of dysregulation of lipid metabolism. The ATP Binding Cassette Transporter (<it>ABCA1</it>) is a key gene involved in lipid metabolism. It encodes the cholesterol regulatory efflux protein which mediates the transfer of cellular phospholipids and cholesterol to acceptor apolipoproteins such as apolipoprotein A-I (ApoA-I). Common polymorphisms in this gene affect High Density Lipoprotein Cholesterol (HDL-C) and Apolipoprotein A-I levels and so influence the risk of atherosclerosis. This study has assessed the distribution of <it>ABCA1 </it>polymorphisms and haplotype arrangements in patients with ischaemic stroke and compared them to an appropriate control group. It also examined the relationship of these polymorphisms with serum lipid profiles in cases and controls.</p> <p>Methods</p> <p>We studied four common polymorphisms in <it>ABCA1 </it>gene: G/A-L158L, G/A-R219K, G/A-G316G and G/A-R1587K in 400 Caucasian ischaemic stroke patients and 487 controls. Dynamic Allele Specific Hybridisation (DASH) was used as the genotyping assay.</p> <p>Results</p> <p>Genotype and allele frequencies of all polymorphisms were similar in cases and controls, except for a modest difference in the <it>ABCA1 </it>R219K allele frequency (P-value = 0.05). Using the PHASE2 program, haplotype frequencies for the four loci (158, 219, 316, and 1587) were estimated in cases and controls. There was no significant difference in overall haplotypes arrangement in patients group compared to controls (p = 0.27). 2211 and 1211 haplotypes (1 = common allele, 2 = rare allele) were more frequent in cases (p = 0.05). Adjusted ORs indicated 40% and 46% excess risk of stroke for these haplotypes respectively. However, none of the adjusted ORs were statistically significant. Individuals who had R219K "22" genotype had a higher LDL level (p = 0.001).</p> <p>Conclusion</p> <p>Our study does not support a major role for the <it>ABCA1 </it>gene as a risk factor for ischaemic stroke. Some haplotypes may confer a minor amount of increased risk or protection. Polymorphisms in this gene may influence serum lipid profile.</p