Document Detail


Genome-wide association with C-reactive protein levels in CLHNS: evidence for the CRP and HNF1A loci and their interaction with exposure to a pathogenic environment.
MedLine Citation:
PMID:  21647738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent genome-wide association studies have related several genetic loci, including C-reactive protein (CRP), hepatocyte nuclear factor 1 homeobox (HNF1A), and genetic variations in the leptin receptor (LEPR), to circulating CRP levels in populations of European ancestry. The genetic effects in other populations and across varying levels of exposure to a pathogenic environment, an important environmental factor associated with CRP, remain to be determined. We tested 2,073,674 single-nucleotide polymorphisms (SNPs) for association with plasma CRP (limited to ≤10 mg/L) in 1,709 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey. The strongest evidence of association was observed with variants at CRP (rs876537, P = 1.4 × 10(-9)) and HNF1A (rs7305618, P = 1.0 × 10(-8)). Among other previously reported CRP-associated loci, the apolipoprotein E ε4 haplotype was associated with decreased CRP level (P = 7.1 × 10(-4)), and modest association was observed with LEPR (rs1892534, P = 0.076), with direction of effects consistent with previous studies. The strongest signal at a locus not previously reported mapped to a gene desert region on chromosome 6q16.1 (rs1408282, P = 2.9 × 10(-6)). Finally, we observed nominal evidence of interaction with exposure to a pathogenic environment for top main effect SNPs at HNF1A (rs7305618, P = 0.031), LEPR (rs1892535, P = 0.030) and 6q16.1 (rs1408282, P = 0.046). Our findings demonstrate convincing evidence that genetic variants in CRP and HNF1A contribute to plasma CRP in Filipino women and provide the first evidence that exposure to a pathogenic environment may modify the genetic influence at the HNF1A, LEPR, and 6q16.1 loci on plasma CRP level.
Authors:
Ying Wu; Thomas W McDade; Christopher W Kuzawa; Judith Borja; Yun Li; Linda S Adair; Karen L Mohlke; Leslie A Lange
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Inflammation     Volume:  35     ISSN:  1573-2576     ISO Abbreviation:  Inflammation     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-29     Completed Date:  2012-08-28     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7600105     Medline TA:  Inflammation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  574-83     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Apolipoprotein E4 / genetics
C-Reactive Protein / analysis,  genetics*
Chromosomes, Human, Pair 6 / genetics*
Female
Genetic Variation
Genome-Wide Association Study*
Genotype
Hepatocyte Nuclear Factor 1-alpha / genetics*
Humans
Inflammation / blood
Philippines
Polymorphism, Single Nucleotide
Receptors, Leptin / genetics*
Grant Support
ID/Acronym/Agency:
DK078150/DK/NIDDK NIH HHS; DK56350/DK/NIDDK NIH HHS; ES10126/ES/NIEHS NIH HHS; HL085144/HL/NHLBI NIH HHS; P20 RR020649/RR/NCRR NIH HHS; P20 RR020649-03/RR/NCRR NIH HHS; P30 DK056350/DK/NIDDK NIH HHS; P30 DK056350-05/DK/NIDDK NIH HHS; P30 ES010126/ES/NIEHS NIH HHS; P30 ES010126-09S1/ES/NIEHS NIH HHS; R01 DK078150/DK/NIDDK NIH HHS; R01 DK078150-04/DK/NIDDK NIH HHS; R01 HD054501/HD/NICHD NIH HHS; R01 HL085144/HL/NHLBI NIH HHS; R01 HL085144-04/HL/NHLBI NIH HHS; R01 TW005596/TW/FIC NIH HHS; R01 TW005596-05/TW/FIC NIH HHS; R24 HD050924/HD/NICHD NIH HHS; RR20649/RR/NCRR NIH HHS; TW05596/TW/FIC NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoprotein E4; 0/HNF1A protein, human; 0/Hepatocyte Nuclear Factor 1-alpha; 0/Receptors, Leptin; 0/leptin receptor, human; 9007-41-4/C-Reactive Protein
Comments/Corrections

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