Toll-like receptor 4 (TLR-4) polymorphisms and asthma risk in rural and urban settings: findings from the UK biobank.

IF 1.6 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Upsala journal of medical sciences Pub Date : 2025-07-04 eCollection Date: 2025-01-01 DOI:10.48101/ujms.v130.12243

Marta A Kisiel, Mathias Rask-Andersen, Åsa Johansson, Weronica E Ek, Anna Rask-Andersen

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引用次数: 0

Abstract

Introduction and aim: 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 TLR4 gene, Asp299Gly and Thr399Ile, and residential area (urban or rural) in females and males with asthma and different asthma phenotypes.

Method: 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.

Result: 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.

Conclusions: Our study found no statistically significant association between TLR4 polymorphisms and asthma, regardless of sex or residential area. Further studies are needed to clarify the functional impact of TLR4 variation in asthma pathophysiology.

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toll样受体4 （TLR-4）多态性与农村和城市环境中的哮喘风险：来自英国生物银行的发现

简介和目的：哮喘的风险及其表型可能被基因-环境相互作用所改变。以往关于细菌内毒素主要受体toll like 4 （TLR4）基因变异与哮喘相互作用的研究，由于研究力度不足，且未考虑不同的哮喘表型，存在矛盾。本研究的主要目的是确定TLR4基因内的两个单核苷酸多态性（snp） Asp299Gly和Thr399Ile与不同哮喘表型的女性和男性哮喘患者的居住区域（城市或农村）之间的相互作用。方法：本研究对来自UK Biobank数据库的38,332名哮喘患者和322,852名非哮喘患者（均为英国高加索人）进行了研究。哮喘也分为表型，如哮喘伴/无过敏和早/晚发型哮喘。居住区以人口面积密度为基础，分为城市和农村居住。采用调整年龄、体重指数和吸烟状况的多变量回归模型分析snp、哮喘居住区域和哮喘表型之间的相互作用。还确定了哮喘与居住区域或snp之间的关系。结果：snp与哮喘风险之间无显著相关性(Asp299Gly: OR (95% CI): 1.00 (0.97-1.02), Thr399Ile: 0.99 (0.96-1.02)， snp与哮喘表型之间在性别或联合队列中均无显著相关性。snp的影响不受住宅区人口密度的影响，无论是哮喘性别还是哮喘表型。哮喘及其表型与snp或居住区域无关。结论：我们的研究发现，TLR4多态性与哮喘之间没有统计学意义上的显著关联，与性别或居住区域无关。TLR4变异在哮喘病理生理中的功能影响尚需进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Upsala journal of medical sciences 医学-医学：内科

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Upsala Journal of Medical Sciences is published for the Upsala Medical Society. It has been published since 1865 and is one of the oldest medical journals in Sweden. The journal publishes clinical and experimental original works in the medical field. Although focusing on regional issues, the journal always welcomes contributions from outside Sweden. Specially extended issues are published occasionally, dealing with special topics, congress proceedings and academic dissertations.