title: Exomic sequencing of immune-related genes reveals novel candidate variants associated with alopecia universalis.
abstract: 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.
authors: Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea.
authors: Seungbok
authors: S
authors: Lee
authors: Seung Hwan
authors: SH
authors: Paik
authors: Hyun-Jin
authors: HJ
authors: Kim
authors: Hyeong Ho
authors: HH
authors: Ryu
authors: Soeun
authors: S
authors: Cha
authors: Seong Jin
authors: SJ
authors: Jo
authors: Hee Chul
authors: HC
authors: Eun
authors: Jeong-Sun
authors: JS
authors: Seo
authors: Jong-Il
authors: JI
authors: Kim
authors: Oh Sang
authors: OS
authors: Kwon
mesh_terms: D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D059472:Exome / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007109:Immunity / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D005819:Genetic Markers