title: Systematic search for single nucleotide polymorphisms in the 5' flanking region of the human phosphodiesterase 3B gene: absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes.
abstract: The activation of phosphodiesterase 3B (PDE3B) reduces free fatty acid output from adipocytes. A reduced PDE3B gene expression could lead to insulin resistance. To determine whether there are polymorphisms associated with type 2 diabetes in PDE3B gene promoter, this 5(') flanking region was isolated. The transcription initiation site was located 206bp upstream from the translation start site. Sequences of 2kb of the 5(') flanking region for 24 type 2 diabetic Japanese subjects were initially analyzed using PCR direct sequencing, and the regions including the identified polymorphisms were then examined. In 98 controls and 98 type 2 diabetic subjects, -1947T>C, -567G>A, -465G>T, -458T>C, and -1727_-1726insTCAATT were found. Only -465G>T and this insertion had more than 5% frequencies. Since a complete linkage disequilibrium existed between them, -465G>T was further analyzed, along with a previously identified +1389G>A in the coding region, in a total of 200 controls and 207 type 2 diabetic subjects. These allele frequencies were not significantly different between these two groups (controls vs. cases; -465G>T, 12.0% vs. 10.1%, P=0.435; +1389G>A, 30.3% vs. 33.3%, P=0.408). These genotype distributions were not significantly different between these two groups. The T/T genotype at -465 was rare although this frequency could be higher in type 2 diabetes (4/207 subjects) than controls (0/200 subjects). The linkage disequilibrium existed between -465G>T and +1389G>A, and the estimated haplotype frequencies defined by these SNPs were not significantly different between the cases and controls. Thus, the identified polymorphisms are unlikely to have major effects on susceptibility to Japanese type 2 diabetes.
authors.affiliation: Department of Laboratory Medicine, Ehime University School of Medicine, Shigenobu, Japan. harosawa@m.ehime-u.ac.jp
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Osawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Niiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onuma
authors.forename: Akiko
authors.initials: A
authors.lastname: Murakami
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ochi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nishimiya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ogura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kato
authors.forename: Ikki
authors.initials: I
authors.lastname: Shimizu
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujii
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamada
authors.forename: Shu-Jian
authors.initials: SJ
authors.lastname: Liang
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Manganiello
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujita-Yamaguchi
authors.forename: Hideichi
authors.initials: H
authors.lastname: Makino
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D024506:5' Flanking Region / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517291:PDE3B protein, human