title: TNF-α gene polymorphisms: association with disease susceptibility and response to anti-TNF-α treatment in psoriatic arthritis.
abstract: The tumor necrosis factor-α (TNF-α) gene has been proposed as a major candidate gene in psoriatic arthritis (PsA). TNF-α is a therapeutic target for patients responding poorly to conventional treatments. We investigated the role of single-nucleotide polymorphisms (SNPs) at positions -238, -308, and +489 of the TNF-α gene in the genetic susceptibility to PsA, in the severity of the disease, and, finally, in the response to TNF-α inhibitors (adalimumab, etanercept, or infliximab). Fifty-seven Caucasian PsA patients and 155 healthy matched controls were studied. The SNP +489 variant allele A was significantly associated with PsA susceptibility (P=0.0136) and severity of clinical (Psoriasis Area and Severity Index score, American College of Rheumatology criteria, Disease Activity Score 28, and Disability Index Health Assessment Questionnaire) and laboratory (C-reactive protein and erythrocyte sedimentation rate) parameters (P-values ranging from 0.016 to 2.908 × 10(-12)). The difference in severity was accounted for by the differences between the AA and GA genotypes with respect to the GG genotype. The SNP +489A allele shows a trend of association with the response to PsA treatment with etanercept. These findings suggest a role of the SNP +489A allele in the susceptibility and severity of PsA.
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. Electronic address: Giuseppe.Murdaca@unige.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Murdaca
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, Section of Medical Genetics, University of Genoa, Genoa, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Gulli
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spanò
authors.affiliation: Biostatistic Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lantieri
authors.affiliation: Dermatology Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Burlando
authors.affiliation: Dermatology Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Parodi
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, Section of Medical Genetics, University of Genoa, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mandich
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Puppo
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000235:genetics*; D016022:Case-Control Studies; D000068800:Etanercept; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept