Kisiel Marta A, Rask-Andersen Mathias, Johansson Åsa, Ek Weronica E, Rask-Andersen Anna
Occupational and Environmental Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Department of Immunology, Genetics and Pathology, Science for Life laboratory, Uppsala University, Uppsala, Sweden.
Ups J Med Sci. 2025 Jul 4;130. doi: 10.48101/ujms.v130.12243. eCollection 2025.
The risk of asthma and its phenotypes may be modified by gene-environmental interactions. The previous studies on the interactions between genetic variations in the toll like 4 (TLR4) the main receptor for bacterial endotoxin, and asthma were contradictory as they were underpowered and did not consider different asthma phenotypes. The main aim of this study was to identify interactions between two single nucleotide polymorphisms (SNPs) within the gene, Asp299Gly and Thr399Ile, and residential area (urban or rural) in females and males with asthma and different asthma phenotypes.
This study was performed on 38,332 asthmatics and 322,852 non-asthma (both British Caucasians) subjects from the UK Biobank database. Asthma was also divided into phenotypes, such as asthma with/without allergy and early/late onset asthma. The residential area was based on the population area density and classified as urban or rural living. Multivariate regression models adjusted for age, body mass index, and smoking status were used to analyze interactions between the SNPs, residential area in asthma, and asthma phenotypes. The association between asthma and residential area or the SNPs was also determined.
There were no significant associations between the SNPs and asthma risk (for Asp299Gly: OR (95% CI): 1.00 (0.97-1.02), for Thr399Ile: 0.99 (0.96-1.02) or between the SNPs and asthma phenotypes in either sex or combined cohorts. The effects of the SNPs were not modified by residential area population density in either sex with asthma or across asthma phenotypes. Asthma and its phenotypes were not associated with the SNPs or residential area.
Our study found no statistically significant association between polymorphisms and asthma, regardless of sex or residential area. Further studies are needed to clarify the functional impact of TLR4 variation in asthma pathophysiology.
哮喘及其表型的风险可能会因基因 - 环境相互作用而改变。先前关于 toll 样受体 4（TLR4，细菌内毒素的主要受体）基因变异与哮喘之间相互作用的研究结果相互矛盾，因为这些研究样本量不足且未考虑不同的哮喘表型。本研究的主要目的是确定哮喘患者及不同哮喘表型的男性和女性中，TLR4 基因内的两个单核苷酸多态性（SNP），即 Asp299Gly 和 Thr399Ile，与居住地区（城市或农村）之间的相互作用。
本研究对来自英国生物银行数据库的38332名哮喘患者和322852名非哮喘患者（均为英国白种人）进行。哮喘也被分为不同表型，如伴有/不伴有过敏的哮喘以及早发型/晚发型哮喘。居住地区根据人口区域密度分为城市或农村居住。使用针对年龄、体重指数和吸烟状况进行调整的多变量回归模型来分析SNP、哮喘患者的居住地区与哮喘表型之间的相互作用。还确定了哮喘与居住地区或SNP之间的关联。
SNP与哮喘风险之间无显著关联（对于Asp299Gly：OR（95%CI）：1.00（0.97 - 1.02），对于Thr399Ile：0.99（0.96 - 1.02）），在任何性别或合并队列中，SNP与哮喘表型之间也无显著关联。在患有哮喘的男性和女性中，以及在不同哮喘表型中，居住地区人口密度均未改变SNP的作用。哮喘及其表型与SNP或居住地区均无关联。
我们的研究发现，无论性别或居住地区如何，TLR4基因多态性与哮喘之间均无统计学上的显著关联。需要进一步研究以阐明TLR4变异在哮喘病理生理学中的功能影响。
