title: Analysis of coding variants in the betacellulin gene in type 2 diabetes and insulin secretion in African American subjects.
abstract: BACKGROUND
  Betacellulin is a member of the epidermal growth factor family, expressed at the highest levels predominantly in the pancreas and thought to be involved in islet neogenesis and regeneration. Nonsynonymous coding variants were reported to be associated with type 2 diabetes in African American subjects. We tested the hypotheses that these previously identified variants were associated with type 2 diabetes in African Americans ascertained in Arkansas and that they altered insulin secretion in glucose tolerant African American subjects.
  
  
  METHODS
  We typed three variants, exon1 Cys7Gly (C7G), exon 2 Leu44Phe (L44F), and exon 4 Leu124Met (L124M), in 188 control subjects and 364 subjects with type 2 diabetes. We tested for altered insulin secretion in 107 subjects who had undergone intravenous glucose tolerance tests to assess insulin sensitivity and insulin secretion.
  
  
  RESULTS
  No variant was associated with type 2 diabetes, and no variant altered insulin secretion or insulin sensitivity. However, an effect on lipids was observed for all 3 variants, and variant L124M was associated with obesity measures.
  
  
  CONCLUSIONS
  We were unable to confirm a role for nonsynonymous variants of betacellulin in the propensity to type 2 diabetes or to impaired insulin secretion.
authors.affiliation: Endocrinology Section, Medical Service, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA. elbeinstevenc@uams.edu
authors.forename: Steven C
authors.initials: SC
authors.lastname: Elbein
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wang
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Karim
authors.forename: Winston S
authors.initials: WS
authors.lastname: Chu
authors.forename: Kristi D
authors.initials: KD
authors.lastname: Silver
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D019943:Amino Acid Substitution; D066259:Betacellulin; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: C587851:BTC protein, human; D066259:Betacellulin; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins