PHF11基因与哮喘或哮喘表型之间不相关---一项在两组不同种群中的研究
2010/01/07
之前曾经有报道人体基因组中有许多区域与哮喘或与哮喘相关的表型有关，然而却鲜少有在特定人群中对上述说法进行重复试验可得到同样的阳性结果的相关报道。此前曾有一些研究报道植物同源结构域锌指蛋白11(homeodomain zinc finger protein 11,PHF11)的基因的变异与血清中IgE水平、哮喘、气道高反应以及儿童特应性皮炎有很强的相关性。为重复此试验，J McClenaghan等人选择了两组不同的人群（n = 2315）作为受试对象，一组是以有孪生子女家庭为单位的研究，含盖了230个家庭（n = 992例），一组是以个人为研究单位的病例对照研究，包括了617例哮喘患者和706例对照人群。收集有关哮喘、呼吸生理、过敏症、环境暴露史等情况，以调查在两组不相关的澳洲西部人群中PHF11基因变异与哮喘和中间基因型之间的关系。研究方法为先用某一个LD标记的20个SNPs定义PHF11基因，应用传递/不平衡检验（TDT）、方差分量模型以及一般线性模型等研究手段来检测PHF11 SNPs与选择的哮喘预后（包括自身肺功能前后的变化）之间的关系。
研究结果发现，对多种检测手段进行校正后，在任何一组人群中均未发现PHF11与哮喘或血清IgE水平之间存在相关性，没有统计学意义(p<0.05)。在每组人群中，也未发现有何哮喘相关的表型与此有关。
J McClenaghan等人进行的研究仍未能复制出之前曾报道的哮喘预后与PHF11相关的说法，且指出在人群中PHF11不太可能具有与哮喘密切相关的靶点。
（于娜 中国医科大学附属第一医院呼吸内科 110001 摘译）
（Thorax 2009;64:620-625）
The PHF11 gene is not associated with asthma or asthma phenotypes in two independent populations
J McClenaghan1, N M Warrington1, E F Jamrozik1, J Hui2,3, J P Beilby2,3, J Hansen4, N H de Klerk4, A L James5,6, A W Musk5,6 and L J Palmer1,7,8
1 Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Nedlands, Australia
2 Clinical Biochemistry, PathWest Laboratory Medicine, Perth, Australia
3 School of Surgery and Pathology, University of Western Australia, Perth, Australia
4 Division of Biostatistics and Genetic Epidemiology, Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia
5 West Australian Sleep Disorders Research Institute, Sir Charles Gardner Hospital, Nedlands, Australia
6 School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia
7 Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Nedlands, Australia
8 School of Population Health, University of Western Australia, Crawley, Australia
Correspondence to:
Professor L J Palmer, University of Western Australia, Nedlands, WA 6009, Australia; lyle@cyllene.uwa.edu.au
Background: Numerous areas of the human genome have previously been associated with asthma and asthma-related phenotypes, but few positive findings have been successfully replicated in independent populations. Initial studies have reported strong associations of variants in the plant homeodomain zinc finger protein 11 (PHF11) gene with serum IgE levels, asthma, airway hyper-responsiveness and childhood atopic dermatitis.
Objectives: To investigate the association of variants in the PHF11 gene with asthma and associated intermediate phenotypes in two independent Western Australian population-based samples.
Methods: A linkage-disequilibrium (LD)-tagging set of 20 single nucleotide polymorphisms (SNPs) was genotyped in PHF11 in two separate populations (total n = 2315), a family-based twin study consisting of 230 families (n = 992 subjects) and a population-based nested case-control study consisting of 617 asthma cases and 706 controls. Information regarding asthma, respiratory physiology, atopy and environmental exposures was collected. Transmission disequilibrium tests, variance components models and generalised linear models were used to test for association between PHF11 SNPs and selected asthma outcomes (including longitudinal change in lung function).
Results: After correction for multiple testing, no statistically significant (p<0.05) associations were found between PHF11 and either asthma or total serum IgE levels in either population. No statistically significant associations were found with any other asthma-associated phenotypes in either population.
Conclusions: Previously reported associations of PHF11 with asthma outcomes were not replicated in this study. This study suggests that PHF11 is unlikely to contain polymorphic loci that have a major impact on asthma susceptibility in our populations.
Published Online First: 21 April 2009. doi:10.1136/thx.2008.108985
Thorax 2009;64:620-625
Copyright © 2009 BMJ Publishing Group Ltd & British Thoracic Society.
ASTHMA
研究结果发现，对多种检测手段进行校正后，在任何一组人群中均未发现PHF11与哮喘或血清IgE水平之间存在相关性，没有统计学意义(p<0.05)。在每组人群中，也未发现有何哮喘相关的表型与此有关。
J McClenaghan等人进行的研究仍未能复制出之前曾报道的哮喘预后与PHF11相关的说法，且指出在人群中PHF11不太可能具有与哮喘密切相关的靶点。
（于娜 中国医科大学附属第一医院呼吸内科 110001 摘译）
（Thorax 2009;64:620-625）
The PHF11 gene is not associated with asthma or asthma phenotypes in two independent populations
J McClenaghan1, N M Warrington1, E F Jamrozik1, J Hui2,3, J P Beilby2,3, J Hansen4, N H de Klerk4, A L James5,6, A W Musk5,6 and L J Palmer1,7,8
1 Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Nedlands, Australia
2 Clinical Biochemistry, PathWest Laboratory Medicine, Perth, Australia
3 School of Surgery and Pathology, University of Western Australia, Perth, Australia
4 Division of Biostatistics and Genetic Epidemiology, Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia
5 West Australian Sleep Disorders Research Institute, Sir Charles Gardner Hospital, Nedlands, Australia
6 School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia
7 Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Nedlands, Australia
8 School of Population Health, University of Western Australia, Crawley, Australia
Correspondence to:
Professor L J Palmer, University of Western Australia, Nedlands, WA 6009, Australia; lyle@cyllene.uwa.edu.au
Background: Numerous areas of the human genome have previously been associated with asthma and asthma-related phenotypes, but few positive findings have been successfully replicated in independent populations. Initial studies have reported strong associations of variants in the plant homeodomain zinc finger protein 11 (PHF11) gene with serum IgE levels, asthma, airway hyper-responsiveness and childhood atopic dermatitis.
Objectives: To investigate the association of variants in the PHF11 gene with asthma and associated intermediate phenotypes in two independent Western Australian population-based samples.
Methods: A linkage-disequilibrium (LD)-tagging set of 20 single nucleotide polymorphisms (SNPs) was genotyped in PHF11 in two separate populations (total n = 2315), a family-based twin study consisting of 230 families (n = 992 subjects) and a population-based nested case-control study consisting of 617 asthma cases and 706 controls. Information regarding asthma, respiratory physiology, atopy and environmental exposures was collected. Transmission disequilibrium tests, variance components models and generalised linear models were used to test for association between PHF11 SNPs and selected asthma outcomes (including longitudinal change in lung function).
Results: After correction for multiple testing, no statistically significant (p<0.05) associations were found between PHF11 and either asthma or total serum IgE levels in either population. No statistically significant associations were found with any other asthma-associated phenotypes in either population.
Conclusions: Previously reported associations of PHF11 with asthma outcomes were not replicated in this study. This study suggests that PHF11 is unlikely to contain polymorphic loci that have a major impact on asthma susceptibility in our populations.
Published Online First: 21 April 2009. doi:10.1136/thx.2008.108985
Thorax 2009;64:620-625
Copyright © 2009 BMJ Publishing Group Ltd & British Thoracic Society.
ASTHMA
上一篇：
VRGF多态性和儿童哮喘、肺功能和气道反应性的关系
下一篇：
喘息住院婴儿嗜酸性粒细胞活性和儿童持续性哮喘风险
