Diabetes Care, Vol 23, Issue 3 302-304, Copyright © 2000 by American Diabetes Association

ARTICLES

Mutations in the genes for hepatocyte nuclear factor (HNF)-1alpha, -4alpha, -1beta, and -3beta; the dimerization cofactor of HNF-1; and insulin promoter factor 1 are not common causes of early-onset type 2 diabetes in Pima Indians

LJ Baier, PA Permana, M Traurig, A Dobberfuhl, C Wiedrich, J Sutherland, P Thuillez, G Luczy-Bachman, M Hara, Y Horikawa, Y Hinokio, RL Hanson and C Bogardus
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Arizona 85016, USA. lbaier@phx.niddk.nih.gov

OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of type 2 diabetes characterized by an early age at onset and autosomal dominant inheritance. MODY can result from heterozygous mutations in at least five genes. The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contribute to the development of early-onset type 2 diabetes in Pima Indians. RESEARCH DESIGN AND METHODS: The coding regions of the known MODY genes hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, HNF-1beta, and insulin promoter factor 1 and the coding regions of two MODY candidate genes, HNF-3beta and the dimerization cofactor of HNF-1, were sequenced in genomic DNA from Pima Indians. The primary "affected" study population consisted of 46 Pima Indians whose age at onset of type 2 diabetes was < or =20 years. DNA sequence variants identified in the affected group were then analyzed in a group of 80 "unaffected" Pima Indians who were at least 40 years old and had normal glucose tolerance. RESULTS: A total of 11 polymorphisms were detected in these genes. However, none of the polymorphisms differed in frequency among Pima Indians with an early age at onset of diabetes compared with older Pima Indians with normal glucose tolerance. CONCLUSIONS: Mutations in these known MODY or MODY candidate genes are not a common cause of early-onset diabetes in Pima Indians.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Krakoff, R. S. Lindsay, H. C. Looker, R. G. Nelson, R. L. Hanson, and W. C. Knowler Incidence of Retinopathy and Nephropathy in Youth-Onset Compared With Adult-Onset Type 2 Diabetes Diabetes Care, January 1, 2003; 26(1): 76 - 81. [Abstract] [Full Text] [PDF]

				W. Pratipanawatr, T. Pratipanawatr, K. Cusi, R. Berria, J. M. Adams, C. P. Jenkinson, K. Maezono, R. A. DeFronzo, and L. J. Mandarino Skeletal Muscle Insulin Resistance in Normoglycemic Subjects With a Strong Family History of Type 2 Diabetes Is Associated With Decreased Insulin-Stimulated Insulin Receptor Substrate-1 Tyrosine Phosphorylation Diabetes, November 1, 2001; 50(11): 2572 - 2578. [Abstract] [Full Text] [PDF]

				J. Krakoff, R. L. Hanson, S. Kobes, and W. C. Knowler Comparison of the Effect of Plasma Glucose Concentrations on Microvascular Disease Between Pima Indian Youths and Adults Diabetes Care, June 1, 2001; 24(6): 1023 - 1028. [Abstract] [Full Text]