An autosomal genomic scan for loci linked to prediabetic phenotypes in pima indians

Richard E. Pratley, D. Bruce Thompson, Michal Prochazka, Leslie Baier, David Mott, Eric Ravussin, Hakan Sakul, Margaret G. Ehm, Daniel K. Burns, Tatiana Foroud, W. Timothy Garvey, Robert L. Hanson, William C. Knowler, Peter H. Bennett, Clifton Bogardus

Research output: Contribution to journalArticle

205 Scopus citations

Abstract

Type 2 diabetes mellitus is a common chronic disease that is thought to have a substantial genetic basis. Identification of the genes responsible has been hampered by the complex nature of the syndrome. Abnormalities in insulin secretion and insulin action predict the development of type 2 diabetes and are, themselves, highly heritable traits. Since fewer genes may contribute to these precursors of type 2 diabetes than to the overall syndrome, such genes may be easier to identify. We, therefore, undertook an autosomal genomic scan to identify loci linked to prediabetic traits in Pima Indians, a population with a high prevalence of type 2 diabetes. 363 nondiabetic Pima Indians were genotyped at 516 polymorphic microsatellite markers on all 22 autosomes. Linkage analyses were performed using three methods (single-marker, nonparametric multipoint [MAPMAKER/SIBS], and variance components multipoint). These analyses provided evidence for linkage at several chromosomal regions, including 3q21-24 linked to fasting plasma insulin concentration and in vivo insulin action, 4p15-q12 linked to fasting plasma insulin concentration, 9q21 linked to 2-h insulin concentration during oral glucose tolerance testing, and 22q12-13 linked to fasting plasma glucose concentration. These results suggest loci that may harbor genes contributing to type 2 diabetes in Pima Indians. None of the linkages exceeded a LOD score of 3.6 (a 5% probability of occurring in a genome-wide scan). These findings must, therefore, be considered tentative until extended in this population or replicated in others.

Original languageEnglish (US)
Pages (from-to)1757-1764
Number of pages8
JournalJournal of Clinical Investigation
Volume101
Issue number8
DOIs
StatePublished - Apr 15 1998

Keywords

  • Genetics
  • Glucose tolerance
  • Insulin action
  • Insulin secretion
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'An autosomal genomic scan for loci linked to prediabetic phenotypes in pima indians'. Together they form a unique fingerprint.

  • Cite this

    Pratley, R. E., Thompson, D. B., Prochazka, M., Baier, L., Mott, D., Ravussin, E., Sakul, H., Ehm, M. G., Burns, D. K., Foroud, T., Garvey, W. T., Hanson, R. L., Knowler, W. C., Bennett, P. H., & Bogardus, C. (1998). An autosomal genomic scan for loci linked to prediabetic phenotypes in pima indians. Journal of Clinical Investigation, 101(8), 1757-1764. https://doi.org/10.1172/JCI1850