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.