Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos

V. Saroja Voruganti, Shelley A. Cole, Sven O.E. Ebbesson, Harald H.H. Göring, Karin Haack, Sandra Laston, Charlotte R. Wenger, M. Elizabeth Tejero, Richard B. Devereux, Richard R. Fabsitz, Jean W. MacCluer, Jason G. Umans, Barbara V. Howard, Anthony G. Comuzzie

    Research output: Contribution to journalArticlepeer-review

    23 Scopus citations

    Abstract

    Background: Alterations in plasma fatty acid distribution are linked to metabolic abnormalities related to type 2 diabetes and cardiovascular disease. Objective: The aim of this study was to investigate genetic factors influencing plasma fatty acid distribution in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Design: Fatty acids in plasma were measured by gas chromatography in 761 related individuals (>35 y of age). Results: Quantitative genetic analyses showed that fatty acid distribution is significantly heritable (P < 0.001), with heritabilities ranging from 0.33 to 0.55. A genome-wide scan for plasma fatty acids identified a 20-cM region on chromosome 8 (p12-p21) with a quantitative trait locus for monounsaturated fatty acids (logarithm of odds score = 3.8). The same region had a quantitative trait locus for polyunsaturated fatty acids (logarithm of odds score = 2.6). We genotyped single nucleotide polymorphisms (SNPs) in candidate genes in 8p12-p21 and found a significant association between fatty acids and SNPs in apolipoprotein J (APOJ), lipoprotein lipase (LPL), macrophage scavenger receptor 1 (MSR1), and tumor necrosis factor receptor superfamily member 10b (TNFRSF10B). A Bayesian quantitative trait nucleotide analysis based on a measured genotype model showed that SNPs in LPL, TNFRSF10B, and APOJ had strong statistical evidence of a functional effect (posterior probability ≥75%) on plasma fatty acid distribution. Conclusions: The results indicate that there is strong genetic influence on plasma fatty acid distribution and that genetic variation in APOJ, LPL, and TNFRSF10B may play a role. The GOCADAN study was registered at www.clinicaltrials.gov as NCT00006192.

    Original languageEnglish (US)
    Pages (from-to)1574-1583
    Number of pages10
    JournalAmerican Journal of Clinical Nutrition
    Volume91
    Issue number6
    DOIs
    StatePublished - Jun 1 2010

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Nutrition and Dietetics

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