Glutathione S-transferase, catalase, and mitochondrial superoxide dismutase gene polymorphisms modulate redox potential in systemic lupus erythematosus patients from Manaus, Amazonas, Brazil

2021 ◽  
Author(s):  
Marco Aurélio Almeida de Oliveira ◽  
Neila Hiraishi Mallmann ◽  
Giselle Katiane Bonfim Bacellar de Souza ◽  
Thiago de Jesus Bacha ◽  
Emerson Silva Lima ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Superoxide Dismutase ◽  
Redox Potential ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Glutathione S Transferase ◽  
Systemic Lupus ◽  
Mitochondrial Superoxide ◽  
Superoxide Dismutase Gene ◽  
Mitochondrial Superoxide Dismutase

scholarly journals THU0017 ATTEMPTS TO LINK EXONIC GENE POLYMORPHISMS TO SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)-ASSOCIATED PROTEIN MODIFIED FUNCTIONALITY: A STRUCTURAL BIOLOGY APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 221.1-222
Author(s):  
E. Eliopoulos ◽  
G. Goulielmos ◽  
M. Matalliotakis ◽  
D. Vlachakis ◽  
T. Niewold ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Protein Structure ◽  
Molecular Modeling ◽  
Nucleic Acid ◽  
Molecular Mechanics ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Association Studies ◽  
Systemic Lupus ◽  
Molecular Graphics

Background:Gene association studies and genome wide association studies (GWAS) have played a primary role in depicting genetic contributions to systemic lupus erythematosus (SLE) development, while accommodating the exonic polymorphisms on the protein structure level, when available, enhances our understanding of protein function modification or depletion. Linking human genetics with therapeutic targets requires the biological function of the causal gene and variant to be known.Objectives:To investigate recently identified SLE-associated functional gene polymorphisms, such asPARP1,ITGAM, TNFAIP3, NCF1, PON1, IFIH1, SH2B3andTYK2[1-4] by correlation to protein structure and function.Methods:Three-dimensional (3D) homology modeling and molecular mechanics/dynamics studies were applied for the localization of the polymorphisms under study on the respective proteins. The mutants were constructed using molecular modeling with the program Maestro (Schrodinger, LLC), which was also used to analyze the conformational changes caused by the mutation. All figures depicting 3D models were created using the molecular graphics program PyMOL V.2.2 [5].Results:Modeling revealed that rs1136410 SNP encodes the less common polymorphism Val762Ala onPARP1that reduces enzymatic activity of Poly(ADP-ribose) polymerase 1 (Figure 1),ITGAMpolymorphism rs1143679 (Arg77His) on Integrin alpha M, component of the macrophage-1 antigen complex affects protein surface recognition,TNFAIP3rs2230926 polymorphism encodes Cys instead of Phe at residue 127 of the ubiquitin editing A20 protein, while rs201802880 polymorphism of the neutrophil cytosolic factor 1 (NCF1) gene modifies the function of the cytosolic subunit of neutrophil NADPH oxidase with the mutation Arg90His.PON1is involved in the oxidative stress process that cause tissue damage observed in SLE and anti-phospholipid syndrome (APS). ThePON1Gln192Arg mutation (rs662 SNP) affects shape and recognition of the ligand recognition site as part of the evolutionary process, whileIFIH1(rs35667974) helicase C domain1 mutant I923V is located on an essential RNA beta loop interacting directly with the nucleic acid (Figure 2). Finally, the rs3184504 SNP ofSH2B3gene generates mutant Arg262Trp on SH2 adapter protein 3, acting as a signaling pathway involved in autoimmune disorders, while inTYK2 gene, one of the Janus kinases, the rs35018800 producing mutant Ala928Val modifies the ADP binding site.Figure 1.Details of the Val762 interaction where V762A mutation occurs in PARP1protein.Figure 2.Nucleic acid interacting IFIH1 helicase beta-loop where I923V mutation occurs (in purple).Conclusion:Based on several examples, we have tried to define a rational link from SLE-associated gene polymorphisms to structure and to modified function, including metagenomic analysis of SNPs, protein crystallography, protein molecular modeling, molecular mechanics and dynamics. Locating, shaping and understanding the target protein interaction interface plays a decisive role in most cases and provides clues for further pharmacological or medical actions [6].References:[1]Hur JW et al (2006). Rheumatology 45:711-7[2]Maiti AK et al (2014). Hum Mol Genet 23:4161-76[3]Shimane K et al (2010). Arthritis Rheum. 62:574-9[4]Linge P et al (2019). Ann Rheum Dis. 2019 Nov 8. pii: annrheumdis-2019-215820[5]Schrödinger LLC: The PyMOL Molecular Graphics System 2016 version 2.2. Available from: pymol.org/2/support.html[6]Plenge RM et al (2013). Nat Rev Drug Discov 12:581–94Disclosure of Interests:None declared

scholarly journals Serum levels and gene polymorphisms of angiopoietin 2 in systemic lupus erythematosus patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jia-Min Wang ◽  
Wang-Dong Xu ◽  
Zhi-Chao Yuan ◽  
Qian Wu ◽  
Jie Zhou ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Serum Levels ◽  
Healthy Individuals ◽  
Systemic Lupus ◽  
Potential Biomarker ◽  
Angiopoietin 2 ◽  
Inflammatory Autoimmune Diseases

AbstractThis study aimed to discuss association between serum Angiopoietin2 (Ang2) levels, Ang2 gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility. It was carried out by 235 SLE, 342 other inflammatory autoimmune diseases patients and 380 healthy individuals. Serum Ang2 levels was examinated by ELISA, and Ang2 rs12674822, rs1823375, rs1868554, rs2442598, rs3739390 and rs734701 polymorphisms were genotyped using KASP. Increased Ang2 concentrations in SLE patients were observed compared with healthy controls and patients with other inflammatory autoimmune diseases. For allelic contrast, except for rs1823375 (P = 0.058) and rs2442598 (P = 0.523), frequencies of alleles for other polymorphisms were significantly different between SLE patients and controls. Genotypes for rs12674822 (TT), rs1868554 (TT, TA and TT+TA), rs734701 (TT) were negatively correlated with SLE susceptibility (OR = 0.564 for rs12674822; OR = 0.572, OR = 0.625, OR = 0.607 for rs1868554; OR = 0.580 for rs734701). Patients carrying rs1868554 T allele and rs3739390 G allele were more likely to develop hematuria (P = 0.039; P = 0.003). The G allele frequencies of rs12674822 and rs2442598 were higher in SLE patients with proteinuria (P = 0.043; P = 0.043). GC genotype frequency of rs3739390 was higher in patients with ds-DNA (+) (P = 0.024). In summary, SLE had increased serum Ang2, which may be a potential biomarker, and the polymorphisms correlated with SLE.

scholarly journals Lack of Association of TYK2 Gene Polymorphisms in Chinese Patients with Systemic Lupus Erythematosus

2011 ◽  
Vol 38 (1) ◽  
pp. 177-178 ◽  
Author(s):  
PHILIP LI ◽  
YUK KWAN CHANG ◽  
KA WAI SHEK ◽  
YU LUNG LAU
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Chinese Patients ◽  
Systemic Lupus

scholarly journals Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus

2007 ◽  
Vol 70 (3) ◽  
pp. 233-237 ◽  
Author(s):  
E. Sánchez ◽  
B. Rueda ◽  
J. L. Callejas ◽  
J. M. Sabio ◽  
N. Ortego-Centeno ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Systemic Lupus ◽  
Interleukin 23

scholarly journals Association of interferon-induced helicase C domain (IFIH1) gene polymorphisms with systemic lupus erythematosus and a relevant updated meta-analysis

2016 ◽  
Vol 15 (4) ◽  
Author(s):  
J. De Azevedo Silva ◽  
S.C. Lima ◽  
C. Addobbati ◽  
R. Moura ◽  
L.A. Cavalcanti Brandão ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Systemic Lupus

scholarly journals Association of Vascular Endothelial Growth Factor A gene polymorphisms with susceptibility to Systemic lupus erythematosus in Iranian population

2019 ◽  
Vol 4 (3) ◽  
pp. 109-120
Author(s):  
Samaneh Soltani ◽  
Saeed Aslani ◽  
Seyedeh Tahereh Faezi ◽  
Ahmadreza Jamshidi ◽  
Elham Farhadi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Iranian Population ◽  
Vascular Endothelial ◽  
Systemic Lupus ◽  
Endothelial Growth Factor

Comprehensive approach to study complement C4 in systemic lupus erythematosus: Gene polymorphisms, protein levels and functional activity

2017 ◽  
Vol 92 ◽  
pp. 125-131 ◽  
Author(s):  
M.W.P. Tsang-A-Sjoe ◽  
I.E.M. Bultink ◽  
L.A. Korswagen ◽  
A. van der Horst ◽  
I. Rensink ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Functional Activity ◽  
Gene Polymorphisms ◽  
Comprehensive Approach ◽  
Systemic Lupus ◽  
Complement C4 ◽  
Protein Levels

scholarly journals Study of DNASE I gene polymorphisms in systemic lupus erythematosus susceptibility

2006 ◽  
Vol 66 (4) ◽  
pp. 560-561 ◽  
Author(s):  
A. Bodano ◽  
A. Gonzalez ◽  
E. Balada ◽  
J. Ordi ◽  
P. Carreira ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Dnase I ◽  
Systemic Lupus ◽  
Systemic Lupus Erythematosus Susceptibility ◽  
I Gene
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