The PDE4D gene encodes the type 4D phosphodiesterase, which degrades cyclic adenosine monophosphate (cAMP), an important signal transduction molecule in all cell types. Polymorphisms within PDE4D have been associated with stroke [14], and bone mineral density [15]. PDE4D is the most dominant phosphodiesterase in the lungs and plays an important role in regulating airway smooth muscle contractility [16] demonstrated by PDE4D knockout mice lacking response to methacholine [17]. A study in a Japanese population reported association of one PDE4D SNP (rs829259) and a haplotype consisting of rs10075508 and one interleukin 13 (IL13) SNP with COPD [18]. SNP rs829259 was not associated with FEV1 in all individuals (P = 0.68) and in smokers (P = 0.21) in our study, and SNP rs10075508 was not genotyped or imputed in SpiroMeta. A recent GWAS has also identified PDE4D as an asthma susceptibility gene [19], however, none of the top 5 SNPs associated with asthma is present in our dataset, and the linkage disequilibrium (LD) with SNPs in SpiroMeta is low, so it is difficult to comment on their contribution to lung function measures in our study.
