Title:Case-control Association Study of Autoimmunity Associated Variants in PDCD1 and Juvenile Idiopathic Arthritis
VOLUME: 13 ISSUE: 3
Author(s):Christina Tejeda, Alaine K. Broadaway, Michael J. Ombrello, Milton R. Brown, Lori A. Ponder, Mina Rohani Pichavant, Gabriel Wang, Sheila Angeles-Han, Aimee Hersh, John Bohnsack, Karen N. Conneely, Michael Epstein and Sampath Prahalad*
Affiliation:Department of Pediatrics Emory University School of Medicine, Atlanta, Department of Human Genetics, Emory University School of Medicine, Atlanta, Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Department of Pediatrics Emory University School of Medicine, Atlanta, Children's Health Care of Atlanta, Atlanta, GA, Department of Pediatrics Emory University School of Medicine, Atlanta, Department of Pediatrics Emory University School of Medicine, Atlanta, Children's Health Care of Atlanta, Atlanta, GA, Division of Pediatric Immunology and Rheumatology, University of Utah, Salt Lake City, Division of Pediatric Immunology and Rheumatology, University of Utah, Salt Lake City, Department of Human Genetics, Emory University School of Medicine, Atlanta, Department of Human Genetics, Emory University School of Medicine, Atlanta, Department of Human Genetics, Emory University School of Medicine, Atlanta
Keywords:Juvenile arthritis, genetics, PDCD1, association, juvenile idiopathic arthritis, single nucleotide polymorphisms.
Abstract:Purpose: Variants in the gene encoding Programmed Cell Death-1 (PDCD1) have been
associated with susceptibility to Systemic Lupus Erythematosus and other autoimmune diseases.
Given that clinically distinct autoimmune phenotypes share common genetic susceptibility factors,
variants in PDCD-1 were tested for a possible association with Juvenile Idiopathic Arthritis (JIA).
Methods: Four Single Nucleotide Polymorphisms (SNPS) in the PDCD1 gene were genotyped and
analyzed: rs7421861, rs11568821, rs10204525, and rs7568402 in 834 cases and 855 controls of
Northern European ancestry. Each variant was examined for possible associations with JIA and
then analyzed for association with JIA categories.
Results: PDCD1 variants showed no association with JIA in the cohort overall (rs7421861 p=0.63,
rs11568821 p=0.13, rs10204525 p=0.31, and rs7568402 p=0.45). Stratification by JIA categories
indicated a significant association between systemic JIA and PDCD1 rs7568402 (OR=0.53,
p=0.0027), which remained significant after 10,000 permutations, but was not replicated in an independent
multi-ethnic systemic JIA cohort. A nominal association between enthesitis-related arthritis
and rs115668821 was also observed (OR=0.22, p=0.012).
Conclusion: Unlike other multiple autoimmune disease associated genetic variants, there was no
association between PDCD1 variants and JIA or JIA categories
