Variants of Signal Transducer and Activator of Transcription 6 Gene and Susceptibility of Atopic Dermatitis

• Main Authors: Nai-Wei Kuo, 郭乃文
• Other Authors: 李永凌
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/84646937196901061492

碩士 === 國立臺灣大學 === 流行病學與預防醫學研究所 === 101 === Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly affecting children and infants. The Signal Transducer and Activator of Transcription 6 (STAT6) genetic variants regulate STAT6 protein which takes roles in allergic pathway. The relationship between STAT6 gene and AD needs further investigation. Methods: This study recruited 5,915 children from public schools in 14 Taiwanese communities. We used Hapmap dataset of Han Chinese to choose four tag SNPs (rs703817, rs324015, rs3024974 and rs324011) by Haploview and investigated the relationship between STAT6 gene and AD. We performed deep sequencing around the variant highly associated with AD and then conducted a second association study in our population. Furthermore, in vitro functional assays were used to verify the significant findings. Results: In our children’s cohort, the variant rs324011 revealed a positive effect on the occurrence of AD (Recessive model: OR=1.6, FDR=0.02; Additive model: OR=1.2, FDR=0.06). After deep sequencing, we identified five new targeted variants around rs324011 (rs167769, rs324012, rs3024948, rs117195019, and rs118014438). Among these variants, rs167769 showed a borderline statistical significance (unadjusted OR=1.21, p=0.07; adjusted OR=1.22, p=0.06). Children with variant rs167769 T allele had a higher risk to suffer from AD. Using in vitro luciferase assay, we also found the polymorphic T allele at rs167769 was associated with higher promoter activity of STAT6 gene. Conclusions: The STAT6 variants rs324011 and rs167769 are associated with AD susceptibility, and the polymorphic T allele at rs167769 would increase promoter activity in vitro.