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10.1136/annrheumdis-2015-208441 http://scihub22266oqcxt.onion/10.1136/annrheumdis-2015-208441 C4949149!4949149 !26783109     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26783109 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Ann+Rheum+Dis 2016 ; 75 (11 ): 2007-2013 Nephropedia Template TP {{tp|p=26783109 |t=2016. Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production |pdf=|usr=}}{{26783109 }} gab.com Text Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production JO: Ann Rheum Dis http://www.kidney.de/pget.php?&tw=1&pmid=26783109 #FOAvip OBJECTIVES: Following up the systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) identification of NMNAT2 at rs2022013, we fine-mapped its 150?kb flanking regions containing NMNAT2 and SMG7 in a 15?292 case-control multi-ancestry population and tested functions of identified variants. METHODS: We performed genotyping using custom array, imputation by IMPUTE 2.1.2 and allele specific functions using quantitative real-time PCR and luciferase reporter transfections. SLE peripheral blood mononuclear cells (PBMCs) were cultured with small interfering RNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA. RESULTS: We confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (p=2.4×10(-8), OR=1.23 (95% CI 1.14 to 1.32)). In complete linkage disequilibrium with rs2702178, rs2275675 in the promoter region robustly associated with SMG7 mRNA levels in multiple expression quantitative trait locus (eQTL) datasets. Its risk allele was dose-dependently associated with decreased SMG7 mRNA levels in PBMCs of 86 patients with SLE and 119 controls (p=1.1×10(-3) and 6.8×10(-8), respectively) and conferred reduced transcription activity in transfected HEK-293 (human embryonic kidney cell line) and Raji cells (p=0.0035 and 0.0037, respectively). As a critical component in the nonsense-mediated mRNA decay pathway, SMG7 could regulate autoantigens including ribonucleoprotein (RNP) and Smith (Sm). We showed SMG7 mRNA levels in PBMCs correlated inversely with ANA titres of patients with SLE (r=-0.31, p=0.01), and SMG7 knockdown increased levels of ANA IgG and chemokine (C-C motif) ligand 19 in SLE PBMCs (p=2.0×10(-5) and 2.0×10(-4), respectively). CONCLUSION: We confirmed NMNAT2 and identified independent SMG7 association with SLE. The inverse relationship between levels of the risk allele-associated SMG7 mRNAs and ANA suggested the novel contribution of mRNA surveillance pathway to SLE pathogenesis. Twit Text FOAVip Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production ????Ann Rheum Dis http://www.kidney.de/pget.php?&tw=1&pmid=26783109 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26783109 #FOAvip English Wikipedia <ref>{{Cite pmid|26783109 }}</ref> Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production #MMPMID26783109 Deng Y ; Zhao J ; Sakurai D ; Sestak AL ; Osadchiy V ; Langefeld CD ; Kaufman KM ; Kelly JA ; James JA ; Petri MA ; Bae SC ; Alarcón-Riquelme ME ; Alarcón GS ; Anaya JM ; Criswell LA ; Freedman BI ; Kamen DL ; Gilkeson GS ; Jacob CO ; Merrill JT ; Gaffney PM ; Sivils KM ; Niewold TB ; Ramsey-Goldman R ; Reveille JD ; Scofield RH ; Stevens AM ; Boackle SA ; Vilá LM ; Sohn II ; Lee S ; Chang DM ; Song YW ; Vyse TJ ; Harley JB ; Brown EE ; Edberg JC ; Kimberly RP ; Cantor RM ; Hahn BH ; Grossman JM ; Tsao BP Ann Rheum Dis 2016[Nov]; 75 (11 ): 2007-2013 PMID26783109 show ga OBJECTIVES: Following up the systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) identification of NMNAT2 at rs2022013, we fine-mapped its 150?kb flanking regions containing NMNAT2 and SMG7 in a 15?292 case-control multi-ancestry population and tested functions of identified variants. METHODS: We performed genotyping using custom array, imputation by IMPUTE 2.1.2 and allele specific functions using quantitative real-time PCR and luciferase reporter transfections. SLE peripheral blood mononuclear cells (PBMCs) were cultured with small interfering RNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA. RESULTS: We confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (p=2.4×10(-8), OR=1.23 (95% CI 1.14 to 1.32)). In complete linkage disequilibrium with rs2702178, rs2275675 in the promoter region robustly associated with SMG7 mRNA levels in multiple expression quantitative trait locus (eQTL) datasets. Its risk allele was dose-dependently associated with decreased SMG7 mRNA levels in PBMCs of 86 patients with SLE and 119 controls (p=1.1×10(-3) and 6.8×10(-8), respectively) and conferred reduced transcription activity in transfected HEK-293 (human embryonic kidney cell line) and Raji cells (p=0.0035 and 0.0037, respectively). As a critical component in the nonsense-mediated mRNA decay pathway, SMG7 could regulate autoantigens including ribonucleoprotein (RNP) and Smith (Sm). We showed SMG7 mRNA levels in PBMCs correlated inversely with ANA titres of patients with SLE (r=-0.31, p=0.01), and SMG7 knockdown increased levels of ANA IgG and chemokine (C-C motif) ligand 19 in SLE PBMCs (p=2.0×10(-5) and 2.0×10(-4), respectively). CONCLUSION: We confirmed NMNAT2 and identified independent SMG7 association with SLE. The inverse relationship between levels of the risk allele-associated SMG7 mRNAs and ANA suggested the novel contribution of mRNA surveillance pathway to SLE pathogenesis. |Alleles [MESH] |American Indian or Alaska Native/genetics [MESH] |Antibodies, Antinuclear/*metabolism [MESH] |Carrier Proteins/*genetics [MESH] |Female [MESH] |Genetic Predisposition to Disease [MESH] |Genome-Wide Association Study [MESH] |Genotyping Techniques [MESH] |HEK293 Cells [MESH] |Hispanic or Latino/genetics [MESH] |Humans [MESH] |Leukocytes, Mononuclear/*immunology [MESH] |Linkage Disequilibrium [MESH] |Lupus Erythematosus, Systemic/*genetics/immunology [MESH] |Male [MESH] |Nicotinamide-Nucleotide Adenylyltransferase/*genetics [MESH] |Pedigree [MESH] |RNA, Messenger/metabolism [MESH] |Real-Time Polymerase Chain Reaction [MESH] |Risk Factors [MESH]Decreased SMG7 expression associates with lupus-risk variants and elev(epmc).pdf DeepDyve Pubget Overpricing