Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

Ravindranath Duggirala, Michael P. Stern, Braxton D. Mitchell, Laurie J. Reinhart, Patricia A. Shipman, Olga C. Uresandi, Wendy K. Chung, Rudolph L. Leibel, C. Nicholas Hales, Peter O'Connell, John Blangero

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    Abstract

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low- income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and ~73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is ~15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans.

    Original languageEnglish (US)
    Pages (from-to)694-703
    Number of pages10
    JournalAmerican Journal of Human Genetics
    Volume59
    Issue number3
    StatePublished - Aug 27 1996

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    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

    Cite this

    Duggirala, R., Stern, M. P., Mitchell, B. D., Reinhart, L. J., Shipman, P. A., Uresandi, O. C., Chung, W. K., Leibel, R. L., Hales, C. N., O'Connell, P., & Blangero, J. (1996). Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7. American Journal of Human Genetics, 59(3), 694-703.