Document Detail


Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos.
MedLine Citation:
PMID:  20410100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 > or =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.
Authors:
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
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-04-21
Journal Detail:
Title:  The American journal of clinical nutrition     Volume:  91     ISSN:  1938-3207     ISO Abbreviation:  Am. J. Clin. Nutr.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-21     Completed Date:  2010-06-10     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0376027     Medline TA:  Am J Clin Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1574-83     Citation Subset:  AIM; IM    
Affiliation:
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA. svorugan@sfbrgenetics.org <svorugan@sfbrgenetics.org>
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00006192
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MeSH Terms
Descriptor/Qualifier:
Cardiovascular Diseases / blood,  genetics*
Clusterin / genetics*,  metabolism
DNA / chemistry,  genetics
Diabetes Mellitus, Type 2 / blood,  genetics*
Fatty Acids, Nonesterified / blood*
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Inuits / genetics*
Lipoprotein Lipase / genetics*,  metabolism
Male
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Quantitative Trait, Heritable
Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics*,  metabolism
Scavenger Receptors, Class A / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
C06 RR013556/RR/NCRR NIH HHS; C06 RR014578/RR/NCRR NIH HHS; C06 RR015456/RR/NCRR NIH HHS; C06 RR017515/RR/NCRR NIH HHS; MH59490/MH/NIMH NIH HHS; U01 HL082490/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Clusterin; 0/Fatty Acids, Nonesterified; 0/MSR1 protein, human; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 0/Scavenger Receptors, Class A; 0/TNFRSF10B protein, human; 9007-49-2/DNA; EC 3.1.1.34/Lipoprotein Lipase
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