S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Journal Papers (저널논문_의학과)
Exomic Sequencing of Immune-Related Genes Reveals Novel Candidate Variants Associated with Alopecia Universalis
- Lee, Seungbok; Paik, Seung Hwan; Kim, Hyun-Jin; Ryu, Hyeong Ho; Cha, Soeun; Jo, Seong Jin; Eun, Hee Chul; Seo, Jeong-Sun; Kim, Jong-Il; Kwon, Oh Sang
- Issue Date
- PUBLIC LIBRARY OF SCIENCE
- PLoS One Vol.8 No.1, p. e53613
- Alopecia areata (AA) is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU) based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p<1.92×10?3). Linkage disequilibrium was observed between some of the most significant SNPs, including rs41559420 of HLA-DRB5 (p<0.001, OR 44.57) and rs28362679 of BTNL2 (p<0.001, OR 30.21). While BTNL2 was reported as a general susceptibility gene of AA previously, HLA-DRB5 has not been implicated in AA. In addition, we found several genetic variants in novel genes (HLA-DMB, TLR1, and PMS2) and discovered an additional locus on HLA-A, a known susceptibility gene of AA. This study provides further evidence for the association of previously reported genes with AA and novel findings such as HLA-DRB5, which might represent a hidden culprit gene for AU.