School of Public Health, Curtin University, Kent St, Bentley, 6102, Western Australia, Australia.
Centre for Genetic Origins of Health and Disease, The University of Western Australia and Curtin University, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia.
Sci Rep. 2017 Jul 24;7(1):6342. doi: 10.1038/s41598-017-06791-y.
The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-α SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.
哮喘和过敏性疾病的患病率在不同人群中分布不均，在西方国家呈上升趋势。在这里，我们研究了环境如何影响遗传同质但地理分离的人群中的基因型-表型关联。我们评估了对应于 8 个基因（ADAM33、ALOX5、LT-α、LTC4S、NOS1、ORMDL3、TBXA2R 和 TNF-α）的 18 个单核苷酸多态性（SNP），以及居住在丹麦西化环境中的因纽特人和居住在格陵兰农村地区的因纽特人这两个群体的肺功能和五种呼吸/过敏情况（既往哮喘、支气管炎、鼻炎、皮炎和特应性）。我们的研究结果表明，肺功能与 ORMDL3 中的遗传变异有关，且多态性与居住地有显著的交互作用。LT-α SNP rs909253 和 rs1041981 与支气管炎风险显著相关。LT-α SNP rs2844484 与皮炎易感性有关，且明显受到居住地的影响。观察到的基因-表型关系仅存在于一个群体中，而不存在于另一个群体中。我们得出结论，与支气管炎和过敏易感性相关的基因型-表型关联取决于环境，环境因素/生活方式改变了遗传易感性，并改变了疾病的遗传效应。
