title: Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos.
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.
  
  
  METHODS
  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.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA. svorugan@sfbrgenetics.org <svorugan@sfbrgenetics.org>
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Sven O E
authors.initials: SO
authors.lastname: Ebbesson
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.forename: Karin
authors.initials: K
authors.lastname: Haack
authors.forename: Sandra
authors.initials: S
authors.lastname: Laston
authors.forename: Charlotte R
authors.initials: CR
authors.lastname: Wenger
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Tejero
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.forename: Richard R
authors.initials: RR
authors.lastname: Fabsitz
authors.forename: Jean W
authors.initials: JW
authors.lastname: MacCluer
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D051152:Clusterin / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism
chemical_list: D051152:Clusterin; D005230:Fatty Acids, Nonesterified; C495139:MSR1 protein, human; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D051117:Scavenger Receptors, Class A; C505639:TNFRSF10B protein, human; D004247:DNA; D008071:Lipoprotein Lipase
references.citation: Cytogenet Cell Genet. 1993;63(1):45-6
references.pmid: 8449037
references.citation: Ann Hum Genet. 1986 May;50(2):181-94
references.pmid: 3435047
references.citation: Nat Genet. 2002 Jul;31(3):241-7
references.pmid: 12053178
references.citation: Am J Hum Genet. 1998 May;62(5):1198-211
references.pmid: 9545414
references.citation: Hum Biol. 2005 Oct;77(5):541-59
references.pmid: 16596940
references.citation: Am J Hum Genet. 2004 Sep;75(3):353-62
references.pmid: 15272419
references.citation: J Biol Chem. 1993 Jan 25;268(3):2120-5
references.pmid: 8093617
references.citation: Pharmacogenomics J. 2007 Feb;7(1):29-37
references.pmid: 16636683
references.citation: Am J Epidemiol. 1995 Sep 1;142(5):469-76
references.pmid: 7677125
references.citation: Hum Biol. 1999 Apr;71(2):197-218
references.pmid: 10222643
references.citation: Int J Circumpolar Health. 2006 Feb;65(1):55-64
references.pmid: 16544648
references.citation: Nat Genet. 2009 Oct;41(10):1088-93
references.pmid: 19734902
references.citation: BMC Med Genet. 2007 Sep 19;8 Suppl 1:S17
references.pmid: 17903299
references.citation: Micron. 2006;37(3):208-22
references.pmid: 16360317
references.citation: Clin Genet. 2001 Oct;60(4):293-300
references.pmid: 11683775
references.citation: PLoS Genet. 2009 Nov;5(11):e1000730
references.pmid: 19936222
references.citation: In Vivo. 2008 Jul-Aug;22(4):537-42
references.pmid: 18712185
references.citation: Am J Clin Nutr. 2003 Jul;78(1):40-6
references.pmid: 12816769
references.citation: J Intern Med. 2001 Oct;250(4):348-60
references.pmid: 11576322
references.citation: EMBO J. 1997 Sep 1;16(17):5386-97
references.pmid: 9311998
references.citation: BMC Proc. 2009 Dec 15;3 Suppl 7:S92
references.pmid: 20018089
references.citation: Metabolism. 2009 Feb;58(2):158-66
references.pmid: 19154947
references.citation: PLoS Genet. 2009 Jan;5(1):e1000338
references.pmid: 19148276
references.citation: Am J Hum Genet. 1996 Jun;58(6):1323-37
references.pmid: 8651310
references.citation: Int J Circumpolar Health. 2003 Dec;62(4):343-62
references.pmid: 14964763
references.citation: Ann Hum Genet. 1982 Oct;46(4):373-83
references.pmid: 6961886
references.citation: Am J Hum Genet. 1997 Sep;61(3):748-60
references.pmid: 9326339
references.citation: Biochem Pharmacol. 2008 Apr 1;75(7):1441-50
references.pmid: 18061141
references.citation: Arch Otolaryngol Head Neck Surg. 2005 May;131(5):407-12
references.pmid: 15897419
references.citation: Clin Chim Acta. 1999 Aug;286(1-2):163-80
references.pmid: 10511290
references.citation: Endocr Relat Cancer. 2010 Jan 29;17(1):R1-17
references.pmid: 19903745
references.citation: Am J Epidemiol. 2008 Dec 1;168(11):1233-46
references.pmid: 18922999
references.citation: Hum Hered. 2006;62(2):97-106
references.pmid: 17047339
references.citation: Int J Obes Relat Metab Disord. 1995 Apr;19(4):270-4
references.pmid: 7627251
references.citation: Endocrinology. 2004 Apr;145(4):1849-59
references.pmid: 14691011
references.citation: Int J Circumpolar Health. 2005 Jun;64(3):206-21
references.pmid: 16050315
references.citation: J Lipid Res. 2009 Jul;50(7):1487-96
references.pmid: 19299407
references.citation: J Lipid Res. 2006 Sep;47(9):1908-14
references.pmid: 16741292
references.citation: Gut. 2007 Aug;56(8):1124-31
references.pmid: 17470478
references.citation: J Clin Invest. 1998 Feb 1;101(3):584-7
references.pmid: 9449691
references.citation: Am J Clin Nutr. 2000 Sep;72(3):723-30
references.pmid: 10966890
references.citation: Ann Clin Lab Sci. 2004 Autumn;34(4):400-4
references.pmid: 15648780
references.citation: Nat Genet. 2009 Oct;41(10):1094-9
references.pmid: 19734903
references.citation: Am J Public Health. 1990 Mar;80(3):282-5
references.pmid: 2305905
references.citation: Am J Clin Nutr. 2003 Jul;78(1):91-8
references.pmid: 12816776
references.citation: Int J Circumpolar Health. 1999 Apr;58(2):108-19
references.pmid: 10429340
references.citation: Nat Genet. 2008 Feb;40(2):161-9
references.pmid: 18193043