The Exon 1 Cys7Gly Polymorphism Within the Betacellulin Gene Is Associated With Type 2 Diabetes in African Americans

K. Silver, M. Tolea, J. Wang, T. I. Pollin, F. Yao, B. D. Mitchell
2005 Diabetes  
In vitro and in vivo studies suggest a role for betacellulin in islet neogenesis and regeneration. Since abnormalities in ␤-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
more » ... ified 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. Diabetes 54:1179 -1184, 2005 RESEARCH DESIGN AND METHODS Betacellulin in fetal pancreas. Human pancreatic tissue from 11 fetuses age 9 -24 weeks (weeks 9, 10, 12, 14, 15, 16, 17, 18, 21, 23, and 24) was obtained through Advanced Bioscience Resources (Alameda, CA). Informed consent for the tissue donation was obtained by the procurement center. Gestational age was determined by crown rump length or fetal foot length. Tissue was sent overnight on ice in RPMI media. On arrival, the specimen was dissected free of nonpancreatic tissue, snap frozen in liquid nitrogen, and stored at Ϫ70°C. Total RNA was prepared using RNAqueous (Ambion, Austin, TX) according to
doi:10.2337/diabetes.54.4.1179 pmid:15793259 fatcat:chxuqwgw6nfkretynisz5x4sdi