A paired sibling analysis of the beta-3 adrenergic receptor and obesity in Mexican Americans

Braxton D. Mitchell, John Blangero, Anthony G. Comuzzie, Laura A. Almasy, Alan R. Shuldiner, Kristi Silver, Michael P. Stern, Jean W. MacCluer, James E. Hixson

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    99 Scopus citations

    Abstract

    The β3 adrenergic receptor, located on chromosome 8, is a regulator of energy expenditure and lipolysis. A missense mutation in this gene, characterized by the replacement of tryptophan by arginine at codon 64 (Trp64Arg), is associated with obesity in some studies. We examined the effect of this variant on obesity in Mexican Americans, using a paired sibling design to minimize variability due to genetic background and a previously identified major susceptibility locus for obesity. We identified 45 sib-pairs that were concordant (identical by descent) for a locus on chromosome 2 which we have shown previously to be tightly linked to obesity in this population. The Trp64Arg variant, detected by PCR-restriction fragment length polymorphism analysis, was present in one sibling within each of the 45 sib-pairs. Presence of the variant was associated with significantly higher values in body mass index (P = 0.04), fat mass (P = 0.04), and waist circumference (P = 0.05). We conclude that the Trp64Arg variant is associated with obesity in this Mexican American population. The paired sibling design probably enhanced our ability to detect the effects of this variant by allowing us to account for variation attributable to another obesity susceptibility locus and to background genes.

    Original languageEnglish (US)
    Pages (from-to)584-587
    Number of pages4
    JournalJournal of Clinical Investigation
    Volume101
    Issue number3
    DOIs
    StatePublished - Feb 1 1998

    Keywords

    • Beta-3-adrenoreceptor
    • Genetics
    • Insulin resistance syndrome
    • Obesity
    • Polymorphism

    ASJC Scopus subject areas

    • Medicine(all)

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    Mitchell, B. D., Blangero, J., Comuzzie, A. G., Almasy, L. A., Shuldiner, A. R., Silver, K., Stern, M. P., MacCluer, J. W., & Hixson, J. E. (1998). A paired sibling analysis of the beta-3 adrenergic receptor and obesity in Mexican Americans. Journal of Clinical Investigation, 101(3), 584-587. https://doi.org/10.1172/JCI512