title: Association of phosphodiesterase 4D gene polymorphisms with chronic obstructive pulmonary disease: relationship to interleukin 13 gene polymorphism.
abstract: Activation of the cyclic AMP (cAMP) signaling pathway leads to the suppression of inflammation in the airways and relaxation of airway smooth muscle. Intracellular cAMP levels are determined by a balance between the activities of adenylate cyclase and phosphodiesterases. We hypothesized that polymorphisms of the phosphodiesterase 4D (PDE4D) gene activate its protein function which leads to the downregulation of cAMP, resulting in the development of chronic obstructive pulmonary disease (COPD). A case-control study was performed using Japanese (96 COPD patients and 61 controls) and Egyptians (106 COPD patients and 72 controls) to investigate the association between the polymorphisms of the PDE4D gene and the development of COPD. Genotyping of all subjects for SNP7 (dbSNP ID, rs10075508), SNP13 (rs829259) and SNP15 (rs702531) in exon 15 of the PDE4D gene was conducted. Furthermore, the distributions of haplotypes consisting of PDE4D polymorphisms and those of interleukin (IL) 4, IL13 and beta2 adrenoceptor were analyzed. The distribution of SNP13 allele frequencies of the PDE4D gene was significantly different between the COPD and control groups in the Japanese population (p = 0.041). In haplotype analysis, haplotypes composed of PDE4D SNP7 and IL13 +2044 G/A in the Japanese population showed significant difference between the patients and controls (pcorr = 0.00048). Thus, SNP13 and haplotypes, SNP7 G/A and IL13 +2044 G/A, may be useful for predicting COPD susceptibility.
authors.affiliation: Department of Pulmonary Medicine, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences and University Hospital, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Homma
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Hegab
authors.forename: Wataru
authors.initials: W
authors.lastname: Saitoh
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nomura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishii
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morishima
authors.forename: Takashi
authors.initials: T
authors.lastname: Iizuka
authors.forename: Takumi
authors.initials: T
authors.lastname: Kiwamoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Hosam H
authors.initials: HH
authors.lastname: Massoud
authors.forename: Hosny M
authors.initials: HM
authors.lastname: Massoud
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Hassanein
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Sekizawa
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D018912:Arabs / Q000235:genetics; D044466:Asian People / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015536:Down-Regulation; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology* / Q000235:genetics
chemical_list: D018793:Interleukin-13; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human