Ann Dermatol.  2018 Jun;30(3):276-283. 10.5021/ad.2018.30.3.276.

Association of CDKAL1 Polymorphisms with Early-Onset Atopic Dermatitis in Koreans

• Heo WI
• Park KY
• Lee MK
• Kim JH
• Moon NJ
• Seo SJ

• KMID: 2419167
• DOI: http://doi.org/10.5021/ad.2018.30.3.276

Abstract

BACKGROUND
Atopic dermatitis (AD) has increased in frequency to rates as high as 20% for children in developed countries. AD is one of the most common childhood diseases and has a complex etiology involving genetic and environmental factors. Thus, a broad understanding of genetic background is needed for early diagnosis of AD.
OBJECTIVE
Identification of candidate functional genetic variants associated with early-onset AD in Koreans.
METHODS
Whole-exome sequencing (WES) was performed in three families. Sanger sequencing was used to validate detected variants in 112 AD patients and 61 controls.
RESULTS
Functional variants were filtered by WES, and then variants related to allergic immune diseases were selected through a literature search. Two candidate non-synonymous single-nucleotide polymorphisms of CDKAL1 (rs77152992) and ERBB2 (rs1058808) were identified, c.1226C>T, p.Pro409Leu, c.3463C>G, and p. Pro1170Ala respectively. A case-control study was performed to determine whether rs77152992 and rs1058808 are candidate risk factors for early-onset AD. rs77152992 was significantly associated with early-onset AD (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.21~0.83; p=0.0133) in allele frequencies. The CC genotype of CDKAL1 had significantly increased risk of AD (OR, 2.16; 95% CI, 1.0~4.6; p=0.0475). rs1058808 had no correlation with AD. Total eosinophil count was significantly increased in AD patients with the CC genotype of CDKAL1 (rs77152992).
CONCLUSION
CDKAL1 (rs77152992) and ERBB2 (rs1058808) were deemed functionally interesting based on WES. Our case-control study suggests that the CC genotype of rs77152992 may be associated with increased eosinophil counts. It may enhance the risk of early-onset AD.

Keyword

Atopic dermatitis; CDKAL1; ERBB2; Whole exome sequencing

MeSH Terms

Case-Control Studies
Child
Dermatitis, Atopic*
Developed Countries
Early Diagnosis
Eosinophils
Gene Frequency
Genetic Background
Genotype
Humans
Immune System Diseases
Risk Factors

Figure

• 

  Fig. 1 The relationship of the CDKAL1 polymorphism with total immunoglobulin E (IgE) and eosinophil counts in atopic dermatitis patients. Dot-plot graphs showing concentrations of total IgE levels (A) and eosinophil counts (B) for the CC and TT+CT genotypes. Data are shown as mean±standard deviation. NS: not significant. *p<0.05 by Mann-Whitney U-test for statistical significance.

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