| Author |
Kim, Kyung Won Myers, Rachel A. Lee, Ji Hyun Igartua, Catherine Lee, Kyung Eun Kim, Yoon Hee Kim, Eun-Jin Yoon, Dankyu Lee, Joo-Shil Hirota, Tomomitsu Tamari, Mayumi Takahashi, Atsushi Kubo, Michiaki Choi, Je-Min Kim, Kyu-Earn Nicolae, Dan L. Ober, Carole Sohn, Myung Hyun |
| Description |
Author Affiliation: Kim KW ( Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Korea); Myers RA ( Department of Human Genetics, University of Chicago, Chicago, Ill.); Lee JH ( Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Korea.); Igartua C ( Department of Human Genetics, University of Chicago, Chicago, Ill.); Lee KE ( Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.); Kim YH ( Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.); Kim EJ ( Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Osong, Korea.); Yoon D ( Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Osong, Korea.); Lee JS ( Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Osong, Korea.); Hirota T ( Laboratory for Respiratory and Allergic Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.); Tamari M ( Laboratory for Respiratory and Allergic Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.); Takahashi A ( Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.); Kubo M ( Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.); Choi JM ( Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.); Kim KE ( Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.); Nicolae DL ( Department of Human Genetics, University of Chicago, Chicago, Ill); Ober C ( Department of Human Genetics, University of Chicago, Chicago, Ill.); Sohn MH ( Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. Electronic address: mhsohn@yuhs.ac.) |
| Abstract |
BACKGROUND: Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases. OBJECTIVE: We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD with allergic sensitization. METHODS: Our study included 246 children with recalcitrant AD and 551 adult control subjects with a negative history of both allergic disease and allergic sensitization. DNA from these subjects was genotyped; sets of common single nucleotide polymorphisms (SNPs) were imputed and used in the GWAS after quality control checks. RESULTS: SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0 × 10(-8)). These associated SNPs are more than 1 Mb from the closest gene, protocadherin (PCDH)9. SNPs at 4 additional loci had P values of less than 1 × 10(-6), including SNPs at or near the neuroblastoma amplified sequence (NBAS; 2p24.3), thymus-expressed molecule involved in selection (THEMIS; 6q22.33), GATA3 (10p14), and S-phase cyclin A-associated protein in the ER (SCAPER; 15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 might be primarily an IgE locus, and analyses of published data demonstrated that SNPs at the 15q24.3 region are expression quantitative trait loci for 2 nearby genes, ISL2 and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), in immune cells. CONCLUSION: Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, 2 key features of AD, and potentially extend our understanding of their role in pathogenesis. |
