Ann Dermatol.  2018 Oct;30(5):529-535. 10.5021/ad.2018.30.5.529.

TSLP Polymorphisms in Atopic Dermatitis and Atopic March in Koreans

Affiliations
  • 1Department of Dermatology, Chung-Ang University Hospital, Seoul, Korea. drseo@cau.ac.kr
  • 2Department of Laboratory Medicine, Chung-Ang University Hospital, Seoul, Korea.
  • 3Department of Ophthalmology, Chung-Ang University Hospital, Seoul, Korea.

Abstract

BACKGROUND
Atopic march (AM) is the progression from atopic dermatitis (AD) to allergic rhinitis and asthma. The development of AD is as high as 20% in children worldwide and continues to increase. AD seems to be caused by both genetic and environmental factors. Recently, polymorphisms of the thymic stromal lymphopoietin (TSLP) gene associated with allergic disorders were reported in ethnic groups from various countries.
OBJECTIVE
Identification of TSLP polymorphisms in Koreans with AD or AM.
METHODS
Whole-exome sequencing was performed in 20 AD and 20 AM patients.
RESULTS
Nine single nucleotide polymorphisms (SNPs) of TSLP were detected (rs191607411, rs3806933, rs2289276, rs2289277, rs2289278, rs139817258, rs11466749, rs11466750, rs10073816). These SNPs have been correlated with susceptibility to allergic diseases in ethnic groups from China, Japan, Turkey, and Costa Rica in previous studies. Remarkably, one of 20 patients in the AD group lacked all SNPs, compared to six of 20 patients in the AM group. Odds ratios showed that Korean patients without the nine TSLP variants had an 8.14 times higher risk of moving from AD to AM. Two haplotype blocks were validated in 60 AD and 59 AM patients using Sanger sequencing. The haplotype blocks (rs3806933 and rs2289276) and (rs11466749 and rs11466750) were in high linkage disequilibrium, respectively (D"²=0.97, D"²=1).
CONCLUSION
The increase of major allele frequency of respective nine TSLP variants may enhance the risk of AM. These data will contribute to improved genetic surveillance system in the early diagnosis technology of allergic disease.

Keyword

Atopic dermatitis; Atopic march; Korean; Polymorphisms; Thymic stromal lymphopoietin

MeSH Terms

Asthma
Child
China
Costa Rica
Dermatitis, Atopic*
Early Diagnosis
Ethnic Groups
Gene Frequency
Haplotypes
Humans
Japan
Linkage Disequilibrium
Odds Ratio
Polymorphism, Single Nucleotide
Rhinitis, Allergic
Turkey

Figure

  • Fig. 1 Pairwise linkage disequilibrium (LD) map for six single nucleotide polymorphisms of thymic stromal lymphopoietin gene. (A) Pairwise D′/LOD and (B) r2 value are indicated as colors. White to red colors (closer to 1) representing the increasing strength of LD.


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