Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy

Contains fulltext : 97006.pdf (publisher's version ) (Open Access)The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc

Catalytic Behavior of Iron-Containing Cubic Spinel in the Hydrolysis and Hydrothermolysis of Ammonia Borane

The paper presents a comparative study of the activity of magnetite (Fe3O4) and copper and cobalt ferrites with the structure of a cubic spinel synthesized by combustion of glycine-nitrate precursors in the reactions of ammonia borane (NH3BH3) hydrolysis and hydrothermolysis. It was shown that the use of copper ferrite in the studied reactions of NH3BH3 dehydrogenation has the advantages of a high catalytic activity and the absence of an induction period in the H2 generation curve due to the activating action of copper on the reduction of iron. Two methods have been proposed to improve catalytic activity of Fe3O4-based systems: (1) replacement of a portion of Fe2+ cations in the spinel by active cations including Cu2+ and (2) preparation of highly dispersed multiphase oxide systems, involving oxide of copper

Effect of Ce/Zr Composition on Structure and Properties of Ce1−xZrxO2 Oxides and Related Ni/Ce1−xZrxO2 Catalysts for CO2 Methanation

Ce1−xZrxO2 oxides (x = 0.1, 0.25, 0.5) prepared via the Pechini route were investigated using XRD analysis, N2 physisorption, TEM, and TPR in combination with density functional theory calculations. The Ni/Ce1−xZrxO2 catalysts were characterized via XRD analysis, SEM-EDX, TEM-EDX, and CO chemisorption and tested in carbon dioxide methanation. The obtained Ce1−xZrxO2 materials were single-phase solid solutions. The increase in Zr content intensified crystal structure strains and favored the reducibility of the Ce1−xZrxO2 oxides but strongly affected their microstructure. The catalytic activity of the Ni/Ce1−xZrxO2 catalysts was found to depend on the composition of the Ce1−xZrxO2 supports. The detected negative effect of Zr content on the catalytic activity was attributed to the decrease in the dispersion of the Ni0 nanoparticles and the length of metal–support contacts due to the worsening microstructure of Ce1−xZrxO2 oxides. The improvement of the redox properties of the Ce1−xZrxO2 oxide supports through cation modification can be negated by changes in their microstructure and textural characteristics

Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

4 páginas, 2 figuras, 2 tablas.-- Spanish Scleroderma Group.Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22–23, rs2056626, P = 2.09 × 10−7 in the discovery samples, P = 3.39 × 10−9 in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 × 10−18), IRF5 (P = 1.86 × 10−13) and STAT4 (P = 3.37 × 10−9) gene regions as SSc genetic risk factors.This work was supported by the following grants: T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). J.M. was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain and in part by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain (J.M.). R.B. is supported by the I3P Consejo Superior de Investigaciones Científicas program funded by the 'Fondo Social Europeo'. B.Z.A. is supported by the Netherlands Organization for Health Research and Development (ZonMW grant 016.096.121). B.K. is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). Genotyping of the Dutch control samples was sponsored by US National Insitutes of Mental Health funding, R01 MH078075 (R.O.A.). The German controls were from the PopGen biobank (to B.K.).Peer reviewe