title: Identification of novel candidate variants including COL6A6 polymorphisms in early-onset atopic dermatitis using whole-exome sequencing.
abstract: BACKGROUND
  The prevalence of atopic dermatitis has increased over the last 10 years. Atopic dermatitis tends to run in families and commonly begins to manifest in childhood. The prevalence of atopic dermatitis is as high as 20% in children. Thus, early diagnosis and treatment of atopic dermatitis are important. Understanding its genetic basis is also needed to facilitate early detection.
  
  
  METHODS
  To identify family-specific candidate genetic variants associated with early-onset atopic dermatitis in Koreans, we carried out whole-exome sequencing of three separate families with this condition. Additional validation was performed in 112 AD patients and 61 controls using Sanger sequencing.
  
  
  RESULTS
  We focused on both common functional variants with a minor allele frequency higher than 1% and rare variants with a minor allele frequency less than 1%. The relevance of the respective variants was supported by a program that could predict whether the mutations resulted in damaged protein function. Fourteen overlapping genes were identified during exome sequencing. Three variants of the COL6A6 gene appeared in all three families and were in close proximity to atopic dermatitis-related loci on chromosome 3q21. The homozygous frequency for the rs16830494 minor allele (AA) and the rs59021909 (TT) allele and the rs200963433 heterozygous (CT) frequency were all higher in AD cases compared to controls in a population-based case-control study.
  
  
  CONCLUSIONS
  Identifying family-specific COL6A6 polymorphisms and genetic variants of other candidate genes associated with AD using WES is a novel approach. Our study suggests that COL6A6 variants may be risk factors for atopic dermatitis. This study provides a genetic basis for early-onset AD diagnosis in Korean patients and the development of new therapies.
  
  
  BACKGROUND
  Trial registration number: IRB NO. C2008030 (133); Name of registry: The collection research of clinical data and patient blood to identify genetic and protein biomarker of atopic dermatitis; Date of registration: 09-July-2008.
  
  
  BACKGROUND
  IRB NO. C2015258 (1716); Name of registry: The collection study of patient blood and clinical data for the development of the prognosis prediction and early diagnosis of atopic dermatitis; Date of registration: 15-jan-2016.
authors.affiliation: Department of Dermatology, Chung-Ang University Hospital, Heukseok-Ro 102, Dongjak-Gu, Seoul, South Korea.
authors.forename: Won Il
authors.initials: WI
authors.lastname: Heo
authors.affiliation: Department of Dermatology, Chung-Ang University Hospital, Heukseok-Ro 102, Dongjak-Gu, Seoul, South Korea.
authors.forename: Kui Young
authors.initials: KY
authors.lastname: Park
authors.affiliation: Department of Dermatology, Chung-Ang University Hospital, Heukseok-Ro 102, Dongjak-Gu, Seoul, South Korea.
authors.forename: Taewon
authors.initials: T
authors.lastname: Jin
authors.affiliation: Department of Laboratory Medicine, Chung-Ang University Hospital, Seoul, South Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Chung-Ang University Hospital, Heukseok-Ro 102, Dongjak-Gu, Seoul, South Korea.
authors.forename: MinJeong
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, South Korea.
authors.forename: Eung Ho
authors.initials: EH
authors.lastname: Choi
authors.affiliation: TheragenEtex Bio Institute Inc., Suwon, South Korea.
authors.forename: Hae-Suk
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Dermatology, St. Vincent's Hospital, College of Medicine, Catholic University of Korea, Suwon, South Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Bae
authors.affiliation: Department of Ophthalmology, Chung-Ang University Hospital, Seoul, South Korea.
authors.forename: Nam Ju
authors.initials: NJ
authors.lastname: Moon
authors.affiliation: Department of Dermatology, Chung-Ang University Hospital, Heukseok-Ro 102, Dongjak-Gu, Seoul, South Korea. drseo@hanafos.com.
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Seo
mesh_terms: D017668:Age of Onset; D024142:Collagen Type VI / Q000235:genetics*; D003876:Dermatitis, Atopic / Q000235:genetics*; D059472:Exome; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: C555240:COL6A6 protein, human; D024142:Collagen Type VI
keywords: Atopic dermatitis; COL6A6; Sanger sequencing; Whole-exome sequencing