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Diabetes 54:1179-1184, 2005
© 2005 by the American Diabetes Association, Inc.

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

Kristi Silver, Magdalena Tolea, Jian Wang, Toni I. Pollin, Flora Yao, and Braxton D. Mitchell

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland

In vitro and in vivo studies suggest a role for betacellulin in islet neogenesis and regeneration. Since abnormalities in ß-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 (GC19GC, Cys7Gly), exon 2 (TC130TC, Leu44Phe), exon 4 (TG370TG, 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.

Address correspondence and reprint requests to Kristi Silver, MD, University of Maryland School of Medicine, 660 W. Redwood St., Rm. 498, Baltimore, MD 21201. E-mail: ksilver{at}medicine.umaryland.edu


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