Clinical Characteristics and Genetic Variations in Early-Onset Atopic Dermatitis Patients
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Background: Hereditary factors contribute to atopic dermatitis (AD) development. We developed the reverse blot hybridization assay (REBA) kit to simultaneously detect variations in skin barrier- and immune response-related genes prevalent in Korean AD patients. Objective: To identify genetic variations and clinical characteristics that could predict early AD development. Methods: We compared AD-related genetic variations between early-onset AD subjects and non-AD controls, and clinical characteristics and genetic variations between early- and late-onset AD subjects. We compared 28 early-onset AD subjects and 57 non-AD controls from a birth cohort and 108 early- (age ≤3 years) and 90 late-onset AD subjects and 189 non-AD controls from a university hospital. Genetic variations were detected via REBA. Results: There were no differences in AD-related genetic variation between early-onset AD subjects and non-AD controls in the birth cohort. When the birth cohort and hospital populations were combined, early-onset AD subjects and non-AD controls showed different frequencies of genetic variations of KLK7, SPINK5 1156, DEFB1, IL5RA, IL12RB1a, and IL12RB1b. No differences in the frequency of genetic variations were observed between early- and late-onset AD subjects. Immunoglobulin E positivity for house dust mites was prevalent in late-onset AD subjects. A family history of atopic diseases was associated with early-onset AD. Conclusion: No AD-related genetic variations could predict early AD development in Koreans, even though neonates with a family history of atopic diseases are likely to develop AD at ≤3 years of age. Environmental exposure may be more important than genetic variation in determining the onset age of AD.
Abstract
Background: Hereditary factors contribute to atopic dermatitis (AD) development. We developed the reverse blot hybridization assay (REBA) kit to simultaneously detect variations in skin barrier- and immune response-related genes prevalent in Korean AD patients. Objective: To identify genetic variations and clinical characteristics that could predict early AD development. Methods: We compared AD-related genetic variations between early-onset AD subjects and non-AD controls, and clinical characteristics and genetic variations between early- and late-onset AD subjects. We compared 28 early-onset AD subjects and 57 non-AD controls from a birth cohort and 108 early- (age ≤3 years) and 90 late-onset AD subjects and 189 non-AD controls from a university hospital. Genetic variations were detected via REBA. Results: There were no differences in AD-related genetic variation between early-onset AD subjects and non-AD controls in the birth cohort. When the birth cohort and hospital populations were combined, early-onset AD subjects and non-AD controls showed different frequencies of genetic variations of KLK7, SPINK5 1156, DEFB1, IL5RA, IL12RB1a, and IL12RB1b. No differences in the frequency of genetic variations were observed between early- and late-onset AD subjects. Immunoglobulin E positivity for house dust mites was prevalent in late-onset AD subjects. A family history of atopic diseases was associated with early-onset AD. Conclusion: No AD-related genetic variations could predict early AD development in Koreans, even though neonates with a family history of atopic diseases are likely to develop AD at ≤3 years of age. Environmental exposure may be more important than genetic variation in determining the onset age of AD.
참고문헌 (25)
- Sullivan M, "Current and emerging concepts in atopic dermatitis pathogenesis", Clin Dermatol, 35, pp.349~353 (2017)
- Barker JN, "Null mutations in the filaggrin gene(FLG)determine major susceptibility to early-onset atopic dermatitis that persists into adulthood", J Invest Dermatol, 127, pp.564~567 (2007)
- Kato A, "Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population", Br J Dermatol, 148, pp.665~669 (2003)
- Vasilopoulos Y, "Genetic association between an AACC insertion in the 3’UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis", J Invest Dermatol, 123, pp.62~66 (2004)
- Kim E, "Single nucleotide polymorphisms and the haplotype in the DEFB1 gene are associated with atopic dermatitis in a Korean population", J Dermatol Sci, 54, pp.25~30 (2009)
- Park HW, "Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction", Thorax, 62, pp.265~269 (2007)
- Namkung JH, "IL-5 and IL-5 receptor alpha polymorphisms are associated with atopic dermatitis in Koreans", Allergy, 62, pp.934~942 (2007)
- Namkung JH, "An association between IL-9 and IL-9 receptor gene polymorphisms and atopic dermatitis in a Korean population", J Dermatol Sci, 62, pp.16~21 (2011)
- Lee SY, "Additive effect between IL-13 polymorphism and cesarean section delivery", prenatal antibiotics use on atopic dermatitis : a birth cohort study(COCOA), 2014, pp.9, e96603~
- Namkung JH, "Association of polymorphisms in genes encoding IL-4, IL-13and their receptors with atopic dermatitis in a Korean population", Exp Dermatol, 20, pp.915~919 (2011)
- Kim E, "Association of the single-nucleotide polymorphism and haplotype of the interleukin 18 gene with atopic dermatitis in Koreans", Clin Exp Allergy, 37, pp.865~871 (2007)
- Yoon NY, "Simultaneous detection of barrier-and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay", Clin Exp Dermatol, 43, pp.430~436 (2018)
- Yang HJ, "The Cohort for Childhood Origin of Asthma and allergic diseases(COCOA)study : design, rationale and methods", BMC Pulm Med, 14, pp.109~ (2014)
- Paternoster L, "Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts", J Allergy Clin Immunol, 141, pp.964~971 (2018)
- Carson CG, "Clinical presentation of atopic dermatitis by filaggrin gene mutation status during the first 7 years of life in a prospective cohort study", PLoS One, 7, pp.e48678~ (2012)
- Brown SJ, "Prevalent and low-frequency null mutations in the filaggrin gene are associated with early-onset and persistent atopic eczema", J Invest Dermatol, 128, pp.1591~1594 (2008)
- Luukkonen TM, "The value of FLG null mutations in predicting treatment response in atopic dermatitis : an observational study in Finnish patients", Acta Derm Venereol, 97, pp.456~463 (2017)
- Wan J, "Influence of FLG mutations and TSLP polymorphisms on atopic dermatitis onset age", Ann Allergy Asthma Immunol, 118, pp.737~738 (2017)
- Greisenegger E, "Analysis of four prevalent filaggrin mutations(R501X, 2282del4, R2447X and S3247X)in Austrian and German patients with atopic dermatitis", J Eur Acad Dermatol Venereol, 24, pp.607~610 (2010)
- Dežman K, "SPINK5 is associated with early-onset and CHI3L1 with late-onset atopic dermatitis", Int J Immunogenet, 44, pp.212~218 (2017)
- Heo WI, "Identification of novel candidate variants including COL6A6polymorphisms in early-onset atopic dermatitis using wholeexome sequencing", BMC Med Genet, 18, pp.8~ (2017)
- Bergmann RL, "Predictability of early atopy by cord blood-IgE and parental history", Clin Exp Allergy, 27, pp.752~760 (1997)
- Takahashi N, "Association of the IL12RB1 promoter polymorphisms with increased risk of atopic dermatitis and other allergic phenotypes", Hum Mol Genet, 14, pp.3149~3159 (2005)
- Szegedi A, "Filaggrin mutations in early-and late-onset atopic dermatitis", Br J Dermatol, 172, pp.320~321 (2015)
- 오혜랑, "Filaggrin Mutation in Korean Patients with Atopic Dermatitis", Yonsei Medical Journal, 58(2), pp.395~400 (2017), 연세대학교의과대학[DOI]