University of Western Australia, Perth, Australia.
Allergy. 2010 Feb;65(2):229-37. doi: 10.1111/j.1398-9995.2009.02145.x. Epub 2009 Oct 1.
Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry.
To accomplish this, two unselected populations of Inuit were recruited, one living in Greenland (n = 618) and the other in Denmark (n = 739). Subjects were genotyped for CD14 C-159T, SCGB1A1 A38G, ADRB2 Arg16Gly and Gln27Glu. The resulting genetic data were analysed for relationships with asthma-related parameters including lung function, ever asthma, atopy, rhinitis and dermatitis.
The results showed contrasting magnitude and direction of genetic associations between the two geographically separate Inuit populations. In Greenland, the ADRB2 16Arg allele was associated with male-specific lower lung function, but in Denmark the same allele was associated with male-specific higher lung function. This allele was also associated with higher incidence of ever asthma in Denmark but not in Greenland. The SCGB1A1 38A allele was associated with lower rhinitis prevalence in Greenland but not in Denmark.
These associations suggest that environment interacts with candidate asthma genes to modulate asthma pathogenesis in the Inuit.
遗传和环境因素及其相互作用是哮喘发病机制的核心。本研究旨在探讨不同宏观环境对具有共同祖先的两个地理位置分离的人群中哮喘基因型-表型关联的影响。
为此，我们招募了两个未选择的因纽特人群，一个居住在格陵兰（n=618），另一个居住在丹麦（n=739）。对受试者进行 CD14 C-159T、SCGB1A1 A38G、ADRB2 Arg16Gly 和 Gln27Glu 的基因分型。对所得遗传数据进行分析，以研究其与与哮喘相关的参数之间的关系，包括肺功能、曾患哮喘、过敏、鼻炎和皮炎。
结果表明，两个地理位置分离的因纽特人群之间的遗传关联具有相反的幅度和方向。在格陵兰，ADRB2 16Arg 等位基因与男性特异性较低的肺功能相关，但在丹麦，相同的等位基因与男性特异性较高的肺功能相关。该等位基因也与丹麦而非格陵兰的曾患哮喘的更高发生率相关。SCGB1A1 38A 等位基因与格陵兰较低的鼻炎患病率相关，但与丹麦无关。
这些关联表明，环境与候选哮喘基因相互作用，调节因纽特人中的哮喘发病机制。
