부산대학교 도서관

Jai-Sing Yang,1,* Ting-Yuan Liu,2,* Yu-Chia Chen,2 Shih-Chang Tsai,3 Yu-Jen Chiu,4,5 Chi-Chou Liao,2 Fuu-Jen Tsai6– 8 1Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404327, Taiwan; 2Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, 404327, Taiwan; 3Department of Biological Science and Technology, China Medical University, Taichung, 406040, Taiwan; 4Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112201, Taiwan; 5Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan; 6School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404333, Taiwan; 7China Medical University Children’s Hospital, Taichung, 404327, Taiwan; 8Department of Medical Genetics, China Medical University Hospital, Taichung, 404327, Taiwan*These authors contributed equally to this workCorrespondence: Fuu-Jen Tsai, Department of Medical Genetics, China Medical University Hospital, No. 2, Yude Road, Taichung City, 404332, Taiwan, Tel +886 422052121, Email d0704@mail.cmuh.org.twPurpose: Alopecia areata (AA) is one of the most prevalent autoimmune diseases affecting humans. Given that hair follicles are immune-privileged, autoimmunity can result in disfiguring hair loss. However, the genetic basis for AA in the Taiwanese population remains unknown.Materials and Methods: A genome-wide association study was conducted using a cohort of 408 AA cases and 8167 controls. To link variants to gene relationships, we used 882 SNPs (P< 1E-05) within 74 genes that were associated with AA group to build the biological networks by IPA software. HLA diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)-R package and chi-square analysis.Results: Seven single nucleotide polymorphisms (SNPs) including LINC02006 (rs531166736, rs187306735), APC (rs112800832_C_CAT), SRP19 (rs139948960, rs144784670), EGFLAM (rs16903975) and LDLRAD3 (rs79874564) were closely associated with the AA phenotype (P< 5E-08). Examination of biological networks revealed that these genomic areas are associated with antigen presentation signaling, B cell and T cell development, Th1 and Th2 activation pathways, Notch signaling, crosstalk signaling between dendritic cells and natural killer cells, and phagosome maturation. Based on human leukocyte antigen (HLA) genotype analysis, four HLA genotypes (HLA-B*15:01-*40:01, HLA-DQA1*01:02-*03:03, HLA-DQA1*01:02, and HLA-DQB1*02:01) were found to be associated with AA (adjusted p-value< 0.05). HLA-DQA1*01:02 is the most significantly related gene in the Taiwanese population (adjusted p-value = 2.09E-05).Conclusion: This study successfully identified susceptibility loci associated with AA in the Taiwanese population. These findings not only shed light on the origins of AA within the Taiwanese context but also contribute to a comprehensive understanding of the genetic factors influencing AA susceptibility.Keywords: alopecia areata, genome-wide association study, network analysis, HLA genotypes