Wentao Jiang

Date of Graduation

2017

Document Type

Thesis

Degree Type

MS

College

Davis College of Agriculture, Natural Resources and Design

Department

Biochemistry

Committee Chair

Jianbo Yao

Committee Co-Chair

Vagner A Benedito

Committee Member

Daniel G Panaccione

Abstract

Occupational Asthma (OA) is a common lung disorder that can be caused or aggravated by exposures and conditions in the work places. Di-isocyanate asthma (DA) is one type of OA. Despite years of research, there are no reliable markers to predict risk or susceptibility for DA. Previous studies have identified 23 candidate single nucleotide polymorphisms (SNPs) that are potentially associated with genes that are related with DA. In this study, we tested the functional relevance of the 23 candidate SNPs (mostly intronic) in several DA-related genes. We hypothesized that some of these SNPs may affect the binding of relevant transcription factors, causing altered expression of these genes. We inserted short DNA fragments (~30 bp) containing the SNPs and long DNA fragments containing multiple SNPs into the pGL3-promoter firefly luciferase reporter vector and transfected them into adenocarcinomas human alveolar basal epithelial cells (A549 cell line). The expression levels of different SNP constructs were measured by luciferase reporter assay. Our results showed that 3 SNPs (rs11571537, rs2287231 and rs2446824) that are located in ATF3, TAR1 and CDH17 genes, respectively, had significant difference in luciferase activities between risk and non-risk alleles (C vs. T for rs11571537, A vs. G for rs2287231, and T vs. C for rs2446824). Our data indicate that the SNPs we found may affect the expression of ATF3, TAR1 and CDH17 genes, which may play important roles in the development of the DA.

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