title: The exon 1 Cys7Gly polymorphism within the betacellulin gene is associated with type 2 diabetes in African Americans.
abstract: In vitro and in vivo studies suggest a role for betacellulin in islet neogenesis and regeneration. Since abnormalities in beta-cell function play a role in the development of type 2 diabetes, a mutation in the betacellulin gene could potentially contribute to the development of type 2 diabetes. Using RT-PCR, we initially determined that betacellulin was expressed in 9- to 24-week-old human fetal pancreas. We then screened the betacellulin gene for mutations in subjects with type 2 diabetes and identified seven polymorphisms in segments encompassing the 5' untranslated region (G-233C, A-226G), exon 1 (TGC19GGC, Cys7Gly), exon 2 (CTC130TTC, Leu44Phe), exon 4 (TTG370ATG, Leu124Met), intron 2 (T-31C), and intron 4 (C-4T). These polymorphisms were genotyped in an expanded set of diabetic case and control subjects. Among African Americans (n = 334), the frequency of the Gly7 allele in exon 1 was 31.9% in diabetic case subjects compared with 45.1% in nondiabetic control subjects (P = 0.0004). Allele frequencies for the other polymorphisms did not differ significantly between African-American case and control subjects. Additionally, there were no significant differences in allele frequencies between case and control subjects among the Caucasian sample (n = 426) for any of the seven polymorphisms, including the Gly7 variant. Further studies will be needed to understand the different roles that betacellulin polymorphisms play in susceptibility to type 2 diabetes in Caucasians and African Americans.
authors.affiliation: Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ksilver@medicine.umaryland.edu
authors.forename: Kristi
authors.initials: K
authors.lastname: Silver
authors.forename: Magdalena
authors.initials: M
authors.lastname: Tolea
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
authors.forename: Flora
authors.initials: F
authors.lastname: Yao
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
mesh_terms: D001741:Black or African American / Q000235:genetics; D066259:Betacellulin; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005091:Exons; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D010179:Pancreas / Q000378:metabolism; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
chemical_list: C587851:BTC protein, human; D066259:Betacellulin; D036341:Intercellular Signaling Peptides and Proteins