title: Determination of IL1 R2, ANTXR2, CARD9, and SNAPC4 single nucleotide polymorphisms in Iranian patients with ankylosing spondylitis.
abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin, while both genetic and environmental factors have been demonstrated to be etiologically involved. Recent genome-wide association and replication studies have suggested that anthrax toxin receptor 2 (ANTXR2), interleukin-1 receptor 2 (IL1R2), caspase recruitment domain-containing protein 9 (CARD9), and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) seem to be associated with AS pathogenesis. This case-control study was performed on 349 unrelated AS patients and 469 age- and gender-matched healthy controls, to investigate whether these non-MHC genes (IL1R2 rs2310173, ANTXR2 rs4333130, CARD9 rs4077515, and SNAPC4 rs3812571) influence the AS risk in Iranian population. ANTXR2 rs4333130 allele C (p = 0.0328; OR 0.744, 95% CI 0.598-0.927) and genotype CC (p = 0.0108; OR 0.273, 95% CI 0.123-0.605) were found to be significantly protective against AS. No other associations were found between AS and studied genes. The association between ANTXR2 rs4333130 and AS was independent of HLA-B27 status. Moreover, we found clinical disease severity scores (BASDAI and BASFI) and pain score were higher in ANTXR2 rs4333130 CT genotype. However, we observed that CARD9 allele C (p = 0.012) and genotype CC (p = 0.012) were significant protective factors against AS only in HLA-B27-negative patients, and IL1R2 rs2310173 genotype GT was mildly protective against AS only in HLA-B27-negative status. These findings support the role of non-MHC pathogenic pathways in susceptibility to AS and warrants more comprehensive studies focusing on these non-MHC pathways for developing novel therapeutic strategies.
authors.affiliation: Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish Island, Iran.|Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Momenzadeh
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. mahmoudim@tums.ac.ir.|Rheumatology Research Center, Shariati Hospital, Kargar Ave., P.O. Box 1411713137, Tehran, Iran. mahmoudim@tums.ac.ir.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maani
authors.initials: M
authors.lastname: Beigy
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Garshasbi
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Vodjdanian
authors.affiliation: Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish Island, Iran. afarazmand@khayam.ut.ac.ir.|Department of Cellular and Molecular Biology, Faculty of Science, University of Tehran, Tehran, Iran. afarazmand@khayam.ut.ac.ir.|Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran. afarazmand@khayam.ut.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Farazmand
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Jamshidi
mesh_terms: D000328:Adult; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000276:immunology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007492:Iran / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C447150:ANTXR2 protein, human; D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human; D004268:DNA-Binding Proteins; D015796:HLA-B27 Antigen; C508592:IL1R2 protein, human; D053574:Receptors, Interleukin-1 Type II; D018000:Receptors, Peptide; C116351:SNAPC4 protein, human; D014157:Transcription Factors
keywords: ANTXR2; Ankylosing spondylitis; CARD9; IL1R2; SNAPC4