Effect of gene polymorphisms in ADAM33, TGFβ1, VEGFA, and PLAUR on asthma in Thai population

Abstract

Background: Most of the asthma susceptibility genes have demonstrated moderate effect. Gene-gene interaction may play a role in asthma. Objectives: To investigate the genetic and gene-gene interaction effects of single nucleotide polymorphisms (SNPs) in the ADAM33, TGFβ1, VEGFA, and PLAUR genes on asthma in Thai population. Methods: Two hundred and fifty control and 250 asthmatic Thai subjects were recruited. Asthma was diagnosed based on symptoms and spirometry assessments using criteria outlined by the American Thoracic Society. Degrees of asthma severity were determined according to guidelines provided by the Global Initiative for Asthma. Asthmatic subjects were subcategorized into the low-severity (n = 106) and high-severity (n = 144) groups. Eleven SNPs in four genes were genotyped, including ADAM33 SNPs (rs528557/S2, rs598418, rs44707/ST+4), TGFβ1 SNPs (rs2241715, rs11466345), VEG-FA SNPs (rs833069, rs3025010), and PLAUR SNPs (rs344781, rs344787, rs2239374, rs2239372). Association analyses between SNPs and asthma, and tests for gene-gene interaction were performed. Results: The ADAM33 rs528557/S2 SNP was found to be associated with asthma according to the additive and dominant models. Comparison between the low-severity group and controls showed the VEGFA rs833069 SNP to be significantly associated with the low-severity group. No gene-gene interactions were observed in this study. Conclusions: The ADAM33 rs528557/S2 and the VEGFA rs833069 SNPs were associated with Thai asthmatics, as well as with other populations worldwide. Further studies are warranted to investigate the use these SNPs as biomarkers for establishing early diagnosis or for predicting future risk of asthma.