Document Detail


Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.
MedLine Citation:
PMID:  23362303     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND- Palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1n-7), and oleic acid (18:1n-9) are major saturated and monounsaturated fatty acids that affect cellular signaling and metabolic pathways. They are synthesized via de novo lipogenesis and are the main saturated and monounsaturated fatty acids in the diet. Levels of these fatty acids have been linked to diseases including type 2 diabetes mellitus and coronary heart disease. METHODS AND RESULTS- Genome-wide association studies were conducted in 5 population-based cohorts comprising 8961 participants of European ancestry to investigate the association of common genetic variation with plasma levels of these 4 fatty acids. We identified polymorphisms in 7 novel loci associated with circulating levels of ≥1 of these fatty acids. ALG14 (asparagine-linked glycosylation 14 homolog) polymorphisms were associated with higher 16:0 (P=2.7×10(-11)) and lower 18:0 (P=2.2×10(-18)). FADS1 and FADS2 (desaturases) polymorphisms were associated with higher 16:1n-7 (P=6.6×10(-13)) and 18:1n-9 (P=2.2×10(-32)) and lower 18:0 (P=1.3×10(-20)). LPGAT1 (lysophosphatidylglycerol acyltransferase) polymorphisms were associated with lower 18:0 (P=2.8×10(-9)). GCKR (glucokinase regulator; P=9.8×10(-10)) and HIF1AN (factor inhibiting hypoxia-inducible factor-1; P=5.7×10(-9)) polymorphisms were associated with higher 16:1n-7, whereas PKD2L1 (polycystic kidney disease 2-like 1; P=5.7×10(-15)) and a locus on chromosome 2 (not near known genes) were associated with lower 16:1n-7 (P=4.1×10(-8)). CONCLUSIONS- Our findings provide novel evidence that common variations in genes with diverse functions, including protein-glycosylation, polyunsaturated fatty acid metabolism, phospholipid modeling, and glucose- and oxygen-sensing pathways, are associated with circulating levels of 4 fatty acids in the de novo lipogenesis pathway. These results expand our knowledge of genetic factors relevant to de novo lipogenesis and fatty acid biology.
Authors:
Jason H Y Wu; Rozenn N Lemaitre; Ani Manichaikul; Weihua Guan; Toshiko Tanaka; Millennia Foy; Edmond K Kabagambe; Luc Djousse; David Siscovick; Amanda M Fretts; Catherine Johnson; Irena B King; Bruce M Psaty; Barbara McKnight; Stephen S Rich; Yii-Der I Chen; Jennifer A Nettleton; Weihong Tang; Stefania Bandinelli; David R Jacobs; Brian L Browning; Cathy C Laurie; Xiangjun Gu; Michael Y Tsai; Lyn M Steffen; Luigi Ferrucci; Myriam Fornage; Dariush Mozaffarian
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2013-01-29
Journal Detail:
Title:  Circulation. Cardiovascular genetics     Volume:  6     ISSN:  1942-3268     ISO Abbreviation:  Circ Cardiovasc Genet     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-17     Completed Date:  2013-10-22     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  101489144     Medline TA:  Circ Cardiovasc Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  171-83     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Chromosomes, Human, Pair 2
Cohort Studies
Coronary Disease / genetics,  metabolism,  pathology
Diabetes Mellitus, Type 2 / genetics,  metabolism,  pathology
Fatty Acids, Monounsaturated / blood*
Female
Genetic Loci
Genome-Wide Association Study*
Genotype
Humans
Linkage Disequilibrium
Lipogenesis / genetics*
Male
Middle Aged
Oleic Acid / blood
Palmitic Acid / blood
Polymorphism, Single Nucleotide
Stearic Acids / blood
Grant Support
ID/Acronym/Agency:
263 MD 821336/MD/NIMHD NIH HHS; 263 MD 9164/MD/NIMHD NIH HHS; 5K01DK082729-02/DK/NIDDK NIH HHS; AG-023629/AG/NIA NIH HHS; AG-027058/AG/NIA NIH HHS; AG-15928/AG/NIA NIH HHS; AG-20098/AG/NIA NIH HHS; DK063491/DK/NIDDK NIH HHS; HHSN268201100005C//PHS HHS; HHSN268201100006C//PHS HHS; HHSN268201100007C//PHS HHS; HHSN268201100008C//PHS HHS; HHSN268201100009C//PHS HHS; HHSN268201100010C//PHS HHS; HHSN268201100011C//PHS HHS; HHSN268201100012C//PHS HHS; HL075366/HL/NHLBI NIH HHS; HL080295/HL/NHLBI NIH HHS; HL087652/HL/NHLBI NIH HHS; HL105756/HL/NHLBI NIH HHS; HSN268200625226C//PHS HHS; N01-HC-05187/HC/NHLBI NIH HHS; N01-HC-15103/HC/NHLBI NIH HHS; N01-HC-35129/HC/NHLBI NIH HHS; N01-HC-45133/HC/NHLBI NIH HHS; N01-HC-45134/HC/NHLBI NIH HHS; N01-HC-45204/HC/NHLBI NIH HHS; N01-HC-45205/HC/NHLBI NIH HHS; N01-HC-48047/HC/NHLBI NIH HHS; N01-HC-48048/HC/NHLBI NIH HHS; N01-HC-48049/HC/NHLBI NIH HHS; N01-HC-48050/HC/NHLBI NIH HHS; N01-HC-55222/HC/NHLBI NIH HHS; N01-HC-75150/HC/NHLBI NIH HHS; N01-HC-85079/HC/NHLBI NIH HHS; N01-HC-85086/HC/NHLBI NIH HHS; N01-HC-85239/HC/NHLBI NIH HHS; N01-HC-95095/HC/NHLBI NIH HHS; N01-HC-95159/HC/NHLBI NIH HHS; N01-HC-95169/HC/NHLBI NIH HHS; N02-HL-6-4278/HL/NHLBI NIH HHS; P30 DK063491/DK/NIDDK NIH HHS; R01 HG004960/HG/NHGRI NIH HHS; R01 HL085710/HL/NHLBI NIH HHS; R01-HL-084099/HL/NHLBI NIH HHS; R01HL071051/HL/NHLBI NIH HHS; R01HL071205/HL/NHLBI NIH HHS; R01HL071250/HL/NHLBI NIH HHS; R01HL071251/HL/NHLBI NIH HHS; R01HL071252/HL/NHLBI NIH HHS; R01HL071258/HL/NHLBI NIH HHS; R01HL071259/HL/NHLBI NIH HHS; R01HL086694/HL/NHLBI NIH HHS; R01HL087641/HL/NHLBI NIH HHS; R01HL59367/HL/NHLBI NIH HHS; RR-024156/RR/NCRR NIH HHS; U01-HG-004424/HG/NHGRI NIH HHS; U01-HG-004446/HG/NHGRI NIH HHS; U01-HG-004729/HG/NHGRI NIH HHS; U01HG004402/HG/NHGRI NIH HHS; UL 1RR033176/RR/NCRR NIH HHS; UL1 TR000124/TR/NCATS NIH HHS; UL1RR025005/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids, Monounsaturated; 0/Stearic Acids; 209B6YPZ4I/palmitoleic acid; 2UMI9U37CP/Oleic Acid; 2V16EO95H1/Palmitic Acid; 4ELV7Z65AP/stearic acid
Comments/Corrections

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