THE INFLUENCE OF GENETIC VARIANTS ON KEY GENES IN ALLERGIC DISEASES

Abstract

The genetic components play vital roles in the occurrence of allergic diseases. From our literature review, we found that SNPs at chromosome 4q shown to be associated with various immune-related disorders. Additionally, arachidonic acid (AA) which is a precursor to eicosanoids has been widely viewed as a pro-inflammatory agent. But the role of the related variants in the occurrence of allergic diseases is unclear. In this study we genotyped the variants on the key genes in the chromosome 4q (NAAA and CXCL9) and AA pathway (COX2, HPGDS, PTGDR and TBXA2R) and used luciferase assay, minigene assay and ELISA assay to test the genes’ expression. Full blood mRNA expression, methylation and lung function data were also collected to characterize the variants’ function. The results showed that subjects bearing the risk genotype have significantly increased expression and lower methylation level, and these were significantly associated with lower lung function. These results proved that several variants at chromosome 4q and AA pathway can accelerate the occurrence of allergic diseases by regulating some key genes’ expression. This thesis provides various underlying mechanisms that may function in genetic associations with allergic diseases.