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 journalArticle

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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
Externally publishedYes

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TNF-Related Apoptosis-Inducing Ligand Receptors
Clusterin
Inuits
Lipoprotein Lipase
Fatty Acids
Single Nucleotide Polymorphism
Quantitative Trait Loci
Coronary Artery Disease
Scavenger Receptors
Monounsaturated Fatty Acids
Chromosomes, Human, Pair 8
Unsaturated Fatty Acids
Gas Chromatography
Type 2 Diabetes Mellitus
Cardiovascular Diseases
Nucleotides
Genotype
Genome

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Voruganti, V. S., Cole, S. A., Ebbesson, S. O. E., Göring, H. H. H., Haack, K., Laston, S., ... Comuzzie, A. G. (2010). Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos. American Journal of Clinical Nutrition, 91(6), 1574-1583. https://doi.org/10.3945/ajcn.2009.28927

Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos. / Voruganti, V. Saroja; Cole, Shelley A.; Ebbesson, Sven O E; Göring, Harald H H; Haack, Karin; Laston, Sandra; Wenger, Charlotte R.; Tejero, M. Elizabeth; Devereux, Richard B.; Fabsitz, Richard R.; MacCluer, Jean W.; Umans, Jason G.; Howard, Barbara V.; Comuzzie, Anthony G.

In: American Journal of Clinical Nutrition, Vol. 91, No. 6, 01.06.2010, p. 1574-1583.

Research output: Contribution to journalArticle

Voruganti, VS, Cole, SA, Ebbesson, SOE, Göring, HHH, Haack, K, Laston, S, Wenger, CR, Tejero, ME, Devereux, RB, Fabsitz, RR, MacCluer, JW, Umans, JG, Howard, BV & Comuzzie, AG 2010, 'Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos', American Journal of Clinical Nutrition, vol. 91, no. 6, pp. 1574-1583. https://doi.org/10.3945/ajcn.2009.28927
Voruganti, V. Saroja ; Cole, Shelley A. ; Ebbesson, Sven O E ; Göring, Harald H H ; Haack, Karin ; Laston, Sandra ; Wenger, Charlotte R. ; Tejero, M. Elizabeth ; Devereux, Richard B. ; Fabsitz, Richard R. ; MacCluer, Jean W. ; Umans, Jason G. ; Howard, Barbara V. ; Comuzzie, Anthony G. / Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos. In: American Journal of Clinical Nutrition. 2010 ; Vol. 91, No. 6. pp. 1574-1583.
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AU - Cole, Shelley A.

AU - Ebbesson, Sven O E

AU - Göring, Harald H H

AU - Haack, Karin

AU - Laston, Sandra

AU - Wenger, Charlotte R.

AU - Tejero, M. Elizabeth

AU - Devereux, Richard B.

AU - Fabsitz, Richard R.

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