Association of genetic variation within UBL5 with phenotypes of metabolic syndrome

Kiymet Bozaoglu, Joanne E. Curran, Kate S. Elliott, Ken R. Walder, Thomas D. Dyer, David L. Rainwater, John L. Vandeberg, Anthony G. Comuzzie, Greg R. Collier, Paul Zimmet, Jean W. MacCluer, Jeremy B. Jowett, John Blangero

    Research output: Contribution to journalArticle

    13 Scopus citations

    Abstract

    The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat. and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON. UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs). one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.

    Original languageEnglish (US)
    Pages (from-to)147-159
    Number of pages13
    JournalHuman Biology
    Volume78
    Issue number2
    DOIs
    StatePublished - Apr 2006

    Keywords

    • BEACON gene
    • Diabetes
    • Dyslipidemia
    • Mauritians
    • Metabolic syndrome
    • Mexican Americans
    • Nauruans
    • San Antonio Family Heart Study
    • UBL5

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Genetics
    • Genetics(clinical)

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  • Cite this

    Bozaoglu, K., Curran, J. E., Elliott, K. S., Walder, K. R., Dyer, T. D., Rainwater, D. L., Vandeberg, J. L., Comuzzie, A. G., Collier, G. R., Zimmet, P., MacCluer, J. W., Jowett, J. B., & Blangero, J. (2006). Association of genetic variation within UBL5 with phenotypes of metabolic syndrome. Human Biology, 78(2), 147-159. https://doi.org/10.1353/hub.2006.0033