ORAI1 Genetic Polymorphisms Associated with the Susceptibility of Atopic Dermatitis in Japanese and Taiwanese Populations

Wei Chiao Chang ,Kaori Tomita,Mayumi Tamari,Koji Ebe,Tomomitsu Hirota,Wei Pin Chang,Satoshi Takeuchi,Masafumi Sakashita,Shigeharu Fujieda,Akihiko Miyatake,Tadao Enomoto,Satoru Doi,Edward Hsi,Masutaka Furue,Hidehisa Saeki,Yusuke Nakamura,Li-Fang Wang,Chih Hung Lee ,Hsin Su Yu ,Wei Chiao Chen ,Suh Hang Hank Juo ,Y.c Chiu ,Chien Hui Hong ,Tetsuji Yamada

doi:10.1371/journal.pone.0029387

Abstract

Atopic dermatitis is a chronic inflammatory skin disease. Multiple genetic and environmental factors are thought to be responsible for susceptibility to AD. In this study, we collected 2,478 DNA samples including 209 AD patients and 729 control subjects from Taiwanese population and 513 AD patients and 1027 control subject from Japanese population for sequencing and genotyping ORAI1. A total of 14 genetic variants including 3 novel single-nucleotide polymorphisms (SNPs) in the ORAI1 gene were identified. Our results indicated that a non-synonymous SNP (rs3741596, Ser218Gly) associated with the susceptibility of AD in the Japanese population but not in the Taiwanese population. However, there is another SNP of ORAI1 (rs3741595) associated with the risk of AD in the Taiwanese population but not in the Japanese population. Taken together, our results indicated that genetic polymorphisms of ORAI1 are very likely to be involved in the susceptibility of AD.

Highlights

Atopic dermatitis (AD) or childhood eczema is a chronic relapsing inflammatory skin disease [1] that usually associated with a family history of atopic disorders such as allergic rhinitis and bronchial asthma [2,3,4]
In Taiwanese population, five ORAI1 tagging single nucleotide polymorphisms (SNPs) with a minor allele frequency .10% in the Han Chinese population were selected from the HapMap database
We screened the polymorphisms of ORAI1 and performed a case-control association study and a haplotype analysis

Summary

Introduction

Atopic dermatitis (AD) or childhood eczema is a chronic relapsing inflammatory skin disease [1] that usually associated with a family history of atopic disorders such as allergic rhinitis and bronchial asthma [2,3,4]. The pathogenesis of AD remains elusive, multiple genetic and environmental factors are thought to contribute to the disease onset [2,3,4]. Genes associated with skin-barrier formation and adaptive immunity have been implicated in the development of AD. Filaggrin (FLG) is essential for the maintenance of the skin-barrier function. Genetic mutations in FLG are significantly associated with the risk of AD and elevated immunoglobulin E (IgE) levels [5]. The results from a genome-wide association study (GWAS) have indicated the complex involvement of multiple loci in the susceptibility of human AD [13]

Methods

Results

Conclusion