Document Detail


Genetic analysis of 16 NMR-lipoprotein fractions in humans, the GOLDN study.
MedLine Citation:
PMID:  23192668     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sixteen nuclear magnetic resonance (NMR) spectroscopy lipoprotein measurements of more than 1,000 subjects of GOLDN study, at fasting and at 3.5 and 6 h after a postprandial fat (PPL) challenge at visits 2 and 4, before and after a 3 weeks Fenofibrate (FF) treatment, were included in 6 time-independent multivariate factor analyses. Their top 1,541 unique SNPs were assessed for association with GOLDN NMR-particles and classical lipids. Several SNPs with -log₁₀ p > 7.3 and MAF ≥ 0.10, mostly intergenic associated with NMR-single traits near genes FAM84B (8q24.21), CRIPT (2p21), ACOXL (2q13), BCL2L11 (2q13), PCDH10 (4q28.3), NXPH1 (7p22), and SLC24A4 (14q32.12) in association with NMR-LDLs; HOMER1 (5q14.2), KIT (4q11-q12), VSNL1 (2p24.3), QPRT (16p11.2), SYNPR (3p14.2), NXPH1 (7p22), NELL1 (11p15.1), and RUNX3 (1p36) with NMR-HDLs; and DOK5-CBLN4-MC3R (20q13), NELL1 (11p15.1), STXBP6 (14q12), APOB (2p24-p23), GPR133 (12q24.33), FAM84B (8q24.21) and NR5A2 (1q32.1) in association with NMR-VLDLs particles. NMR single traits associations produced 75 % of 114 significant candidates, 7 % belonged to classical lipids and 18 % overlapped, and 16 % matched for time of discovery between NMR- and classical traits. Five proxy genes, (ACOXL, FAM84B, NXPH1, STK40 and VAPA) showed pleiotropic effects. While tagged for significant associations in our study and with some extra evidence from the literature, candidates as CBNL4, FAM84B, NXPH1, SLC24A4 remain unclear for their functional relation to lipid metabolism. Although GOLDN study is one of the largest in studying PPL and FF treatment effects, the relatively small samples (over 700-1,000 subjects) in association tests appeals for a replication of such a study. Thus, further investigation is needed.
Authors:
Aldi T Kraja; Ingrid B Borecki; Michael Y Tsai; Jose M Ordovas; Paul N Hopkins; Chao-Qiang Lai; Alexis C Frazier-Wood; Robert J Straka; James E Hixson; Michael A Province; Donna K Arnett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-29
Journal Detail:
Title:  Lipids     Volume:  48     ISSN:  1558-9307     ISO Abbreviation:  Lipids     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-07-03     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0060450     Medline TA:  Lipids     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  155-65     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Fasting
Female
Fenofibrate / therapeutic use*
Genome-Wide Association Study
Genotype
Humans
Hypolipidemic Agents / therapeutic use*
Lipoproteins / blood,  genetics*,  metabolism*
Male
Middle Aged
Multivariate Analysis
Nuclear Magnetic Resonance, Biomolecular / methods*
Polymorphism, Single Nucleotide
Postprandial Period / drug effects*
Grant Support
ID/Acronym/Agency:
R01 HL091357/HL/NHLBI NIH HHS; R01 HL09135701/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hypolipidemic Agents; 0/Lipoproteins; U202363UOS/Fenofibrate
Comments/Corrections

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