title: Genetic variation in phosphodiesterase (PDE) 7B in chronic lymphocytic leukemia: overview of genetic variants of cyclic nucleotide PDEs in human disease.
abstract: Expression of cyclic adenosine monophosphate-specific phosphodiesterase 7B (PDE7B) mRNA is increased in patients with chronic lymphocytic leukemia (CLL), thus suggesting that variation may occur in the PDE7B gene in CLL. As genetic variation in other PDE family members has been shown to associate with numerous clinical disorders (reviewed in this manuscript), we sought to identify single-nucleotide polymorphisms (SNPs) in the PDE7B gene promoter and coding region of 93 control subjects and 154 CLL patients. We found that the PDE7B gene has a 5' non-coding region SNP -347C>T that occurs with similar frequency in CLL patients (1.9%) and controls (2.7%). Tested in vitro, -347C>T has less promoter activity than a wild-type construct. The low frequency of this 5' untranslated region variant indicates that it does not explain the higher PDE7B expression in patients with CLL but it has the potential to influence other settings that involve a role for PDE7B.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0636, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Peiró
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Tang
authors.forename: Fiona
authors.initials: F
authors.lastname: Murray
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Zhang
authors.forename: Loren M
authors.initials: LM
authors.lastname: Brown
authors.forename: Daisy
authors.initials: D
authors.lastname: Chou
authors.forename: Laura
authors.initials: L
authors.lastname: Rassenti
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kipps
authors.forename: Paul A
authors.initials: PA
authors.lastname: Insel
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517463:PDE7B protein, human