Association of DOCK8, IL17RA, and KLK12 Polymorphisms with Atopic Dermatitis in Koreans
4
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Early-onset and severe atopic dermatitis (AD) in patients increase the probability of the development of allergic rhinitis or asthma. Treatment and prevention strategies in infants and young children with AD are targeted toward treating the symptoms, restoring skin barrier functions, and reducing the absorption of environmental allergens in an attempt to attenuate or block the onset of asthma and food allergy. Objective: Given that the initiating events in AD remain poorly understood, identifying those at risk and implementing strategies to prevent AD is necessary. Methods: Whole-exome sequencing (WES) was performed in a 43 control group and a disease group with 20 AD patients without atopic march (AM) and 20 with AM. Sanger sequencing was carried out to validate found variants in cohorts. Results: DOCK8, IL17RA, and KLK12 single-nucleotide polymorphisms were identified by WES as missense mutations: c.1289C＞ A, p.P97T (rs529208); c.1685C＞A, p.P562G (rs12484684); and c.457+27＞C, rs3745540, respectively. A case-control study show that total immunoglobulin E (IgE) level was significantly increased in the AA genotype of DOCK8 compared to the CA genotype in allergic patients. The rs12484684 of IL17RA increased risk of adult-onset AD (odds ratio: 1.63) compared to the control for (A) allele frequency. AD and AM Patients with the IL17RA CA genotype also had elevated IgE levels. rs3745540 of KLK12 was associated with AD in dominant model (odds ratio: 2.86). Conclusion: DOCK8 (rs529208), IL17RA (rs12484684), and KLK12 (rs3745540), were identified using a new WES filtering method. the result suggests that polymorphism of DOCK8 and IL17RA might be related to increase the total IgE level.
Abstract
Background: Early-onset and severe atopic dermatitis (AD) in patients increase the probability of the development of allergic rhinitis or asthma. Treatment and prevention strategies in infants and young children with AD are targeted toward treating the symptoms, restoring skin barrier functions, and reducing the absorption of environmental allergens in an attempt to attenuate or block the onset of asthma and food allergy. Objective: Given that the initiating events in AD remain poorly understood, identifying those at risk and implementing strategies to prevent AD is necessary. Methods: Whole-exome sequencing (WES) was performed in a 43 control group and a disease group with 20 AD patients without atopic march (AM) and 20 with AM. Sanger sequencing was carried out to validate found variants in cohorts. Results: DOCK8, IL17RA, and KLK12 single-nucleotide polymorphisms were identified by WES as missense mutations: c.1289C＞ A, p.P97T (rs529208); c.1685C＞A, p.P562G (rs12484684); and c.457+27＞C, rs3745540, respectively. A case-control study show that total immunoglobulin E (IgE) level was significantly increased in the AA genotype of DOCK8 compared to the CA genotype in allergic patients. The rs12484684 of IL17RA increased risk of adult-onset AD (odds ratio: 1.63) compared to the control for (A) allele frequency. AD and AM Patients with the IL17RA CA genotype also had elevated IgE levels. rs3745540 of KLK12 was associated with AD in dominant model (odds ratio: 2.86). Conclusion: DOCK8 (rs529208), IL17RA (rs12484684), and KLK12 (rs3745540), were identified using a new WES filtering method. the result suggests that polymorphism of DOCK8 and IL17RA might be related to increase the total IgE level.
참고문헌 (27)
- Bantz SK, "The atopic march : progression from atopic dermatitis to allergic rhinitis and asthma", J Clin Cell Immunol, 5, pp.202~ (2014)
- Thomsen SF, "Atopic dermatitis: natural history, diagnosis, and treatment", ISRN Allergy, 2014, pp.354250~ (2014)
- Peng W, "Recent developments in atopic dermatitis", Curr Opin Allergy Clin Immunol, 14, pp.417~422 (2014)
- 편복양, "Natural History and Risk Factors of Atopic Dermatitis in Children", Allergy, Asthma & Immunology Research, 7(2), pp.101~105 (2015), 대한천식알레르기학회
- Zaniboni MC, "Skin barrier in atopic dermatitis : beyond filaggrin", An Bras Dermatol, 91, pp.472~478 (2016)
- Uehara M, "Descendant family history of atopic dermatitis", Acta Derm Venereol, 73, pp.62~63 (1993)
- Li K, "FLG mutations in the East Asian atopic dermatitis patients : genetic and clinical implication", Exp Dermatol, 25, pp.816~818 (2016)
- Retterer K, "Clinical application of whole-exome sequencing across clinical indications", Genet Med, 18, pp.696~704 (2016)
- Rabbani B, "The promise of wholeexome sequencing in medical genetics", J Hum Genet, 59, pp.5~15 (2014)
- Carson AR, "Effective filtering strategies to improve data quality from population-based whole exome sequencing studies", BMC Bioinformatics, 15, pp.125~ (2014)
- 허원일, "Association of CDKAL1 Polymorphisms with Early-Onset Atopic Dermatitis in Koreans", Annals of Dermatology, 30(3), pp.276~283 (2018), 대한피부과학회
- Thomas PD, "Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: evolutionary evidence for differences in molecular effects", Proc Natl Acad Sci U S A, 101, pp.15398~15403 (2004)
- Williams HC, "The U.K. working party's diagnostic criteria for atopic dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis", Br J Dermatol, 131, pp.383~396 (1994)
- Zhang W, "Whole genome sequencing of 35 individuals provides insights into the genetic architecture of Korean population", BMC Bioinformatics, 15(Suppl 11), pp.S6~ (2014)
- Garmhausen D, "Characterization of different courses of atopic dermatitis in adolescent and adult patients", Allergy, 68, pp.498~506 (2013)
- Li H, "Fast and accurate short read alignment with Burrows-Wheeler transform", Bioinformatics, 25, pp.1754~1760 (2009)
- DePristo MA, "A framework for variation discovery and genotyping using next-generation DNA sequencing data", Nat Genet, 43, pp.491~498 (2011)
- Cibulskis K, "Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples", Nat Biotechnol, 31, pp.213~219 (2013)
- Marenholz I, "Meta-analysis identifies seven susceptibility loci involved in the atopic march", Nat Commun, 6, pp.8804~ (2015)
- Siepel A, "Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes", Genome Res, 15, pp.1034~1050 (2005)
- Boos AC, "Atopic dermatitis, STAT3- and DOCK8-hyper-IgE syndromes differ in IgE-based sensitization pattern", Allergy, 69, pp.943~953 (2014)
- Engelhardt KR, "Large deletions and point mutations involving the dedicator of cytokinesis 8(DOCK8)in the autosomal-recessive form of hyper-IgE syndrome", J Allergy Clin Immunol, 124, pp.1289~1302.e4 (2009)
- Scirica CV, "Predictors of cord blood IgE levels in children at risk for asthma and atopy", J Allergy Clin Immunol, 119, pp.81~88 (2007)
- Herberth G, "Reduced IFN-gamma-and enhanced IL-4-producing CD4+ cord blood T cells are associated with a higher risk for atopic dermatitis during the first 2 yr of life", Pediatr Allergy Immunol, 21(1 Pt 1), pp.5~13 (2010)
- Laske N, "Does the severity of atopic dermatitis correlate with serum IgE levels?", Pediatr Allergy Immunol, 15, pp.86~88 (2004)
- Floudas A, "IL-17 receptor A maintains and protects the skin barrier to prevent allergic skin inflammation", J Immunol, 199, pp.707~717 (2017)
- Komatsu N, "Expression and localization of tissue kallikrein mRNAs in human epidermis and appendages", J Invest Dermatol, 121, pp.542~549 (2003)