title: Molecular scanning of the betacellulin gene for mutations in type 2 diabetic patients.
abstract: Betacellulin (BTC), a member of the epidermal growth factor (EGF) family, is an important factor in the growth and/or differentiation of pancreatic beta cells. In this point of view, we determined the transcriptional start site of the human BTC gene and screened the protein-coding region for mutations. The transcriptional start site was located 347 bp upstream from the translational initiation codon. After screening the protein coding exons (exons 1-5), we identified two novel missense mutations, Cys (TGC) to Gly (GGC) at codon 7 (C7G) and Leu (TTG) to Met (ATG) at codon 124 (L124M), and a single nucleotide substitution (-31c/t) in the intron 2. The C7G was located in the signal peptide and the L124M in the transmembrane domain and this Leu at codon 124 was conserved among human, bovine, rat, and mouse. The frequencies of these variants, however, were similar between type 2 diabetic patients (n = 228) and non-diabetic control subjects (n = 170). These data suggest that genetic variations in the protein-coding region of the human BTC gene are unlikely to be a major contributor to development of type 2 diabetes.
authors.affiliation: The First Department of Medicine, Wakayama University of Medical Science, 811-1 Kimiidera, Wakayama 641-8509, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Hiroto
authors.initials: H
authors.lastname: Furuta
authors.forename: Tokio
authors.initials: T
authors.lastname: Sanke
authors.forename: Setuya
authors.initials: S
authors.lastname: Sakagashira
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimomura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shimajiri
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hanabusa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Kishio
authors.initials: K
authors.lastname: Nanjo
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D066259:Betacellulin; D003545:Cysteine; D003596:Cytosine; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D005998:Glycine; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007930:Leucine; D008297:Male; D008715:Methionine; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D013941:Thymine; D024363:Transcription Initiation Site
chemical_list: C587851:BTC protein, human; D066259:Betacellulin; C587852:Btc protein, mouse; C587853:Btc protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D003596:Cytosine; D008715:Methionine; D007930:Leucine; D003545:Cysteine; D013941:Thymine; D005998:Glycine