Thongngarm Torpong, Jameekornrak Aree, Chaiyaratana Nachol, Thongnoppakhun Wanna, Sangasapaviliya Atik, Jirapongsananuruk Orathai, Limwongse Chanin
Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Electrical and Computer Engineering, Faculty of Engineering, King Mongkut's University of Technology North Bangkok, Bangkok, Thailand.
Asian Pac J Allergy Immunol. 2022 Mar;40(1):39-46. doi: 10.12932/AP-010419-0532.
Most of the asthma susceptibility genes have demonstrated moderate effect. Gene-gene interaction may play a role in asthma.
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.
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), VEGFA SNPs (rs833069, rs3025010), and PLAUR SNPs (rs344781, rs344787, rs2239374, rs2239372). Association analyses between SNPs and asthma, and tests for gene-gene interaction were performed.
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.
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.
大多数哮喘易感基因已显示出中等效应。基因-基因相互作用可能在哮喘中起作用。
研究ADAM33、TGFβ1、VEGFA和PLAUR基因中的单核苷酸多态性(SNP)对泰国人群哮喘的遗传及基因-基因相互作用效应。
招募了250名对照者和250名哮喘泰国受试者。根据美国胸科学会概述的标准,基于症状和肺功能测定评估来诊断哮喘。根据全球哮喘防治创议提供的指南确定哮喘严重程度。哮喘受试者被分为低严重程度组(n = 106)和高严重程度组(n = 144)。对四个基因中的11个SNP进行基因分型,包括ADAM33 SNP(rs528557/S2、rs598418、rs44707/ST+4)、TGFβ1 SNP(rs2241715、rs11466345)、VEGFA SNP(rs833069、rs3025010)和PLAUR SNP(rs344781、rs344787、rs2239374、rs2239372)。进行了SNP与哮喘之间的关联分析以及基因-基因相互作用测试。
根据加性和显性模型,发现ADAM33 rs528557/S2 SNP与哮喘相关。低严重程度组与对照组之间的比较显示,VEGFA rs833069 SNP与低严重程度组显著相关。本研究未观察到基因-基因相互作用。
ADAM33 rs528557/S2和VEGFA rs833069 SNP与泰国哮喘患者以及全球其他人群相关。有必要进一步研究将这些SNP用作生物标志物以建立早期诊断或预测哮喘未来风险的用途。