Rationale: 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 immunoglobulin E 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=2,315): a family-based twin study consisting of 992 individuals; and a population-based, nested case-control study consisting of 1,323 unrelated subjects. Information regarding asthma, respiratory physiology, atopy, and environmental exposures was collected. Transmission disequilibrium tests, variance components models and generalized linear models were used to test for association between PHF11 SNPs and selected asthma outcomes (including longitudinal change in lung function).
Measurements and main results: Several marginally significant associations were found between PHF11 and spirometry measures and asthma in the Busselton population, however these findings did not remain significant after adjustment for multiple testing. No other significant associations were found with 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.