Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate

Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewid...

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Published inBiology (Basel, Switzerland) Vol. 3; no. 3; pp. 536 - 550
Main Authors Frazier-Wood, Alexis C, Wojczynski, Mary K, Borecki, Ingrid B, Hopkins, Paul N, Lai, Chao-Qiang, Ordovas, Jose M, Straka, Robert J, Tsai, Micheal Y, Tiwari, Hemant K, Arnett, Donna K
Format Journal Article
LanguageEnglish
Published Switzerland MDPI 25.08.2014
MDPI AG
Subjects
candidate gene study
fenofibrate
genetic risk score
GOLDN
HDL size
LDL size
lipoprotein
NMR
particle size
pharmacogenetics
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Abstract Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 (p < 0.004). Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p < 0.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels.
AbstractList Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 ( p < 0.004). Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures ( p < 0.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels.
Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 (p < 0.004). Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p < 0.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels.
Author Wojczynski, Mary K
Tsai, Micheal Y
Lai, Chao-Qiang
Arnett, Donna K
Borecki, Ingrid B
Frazier-Wood, Alexis C
Tiwari, Hemant K
Ordovas, Jose M
Hopkins, Paul N
Straka, Robert J
AuthorAffiliation 5 The Department of Epidemiology and Population Genetics. Centro Nacional Investigación Cardiovasculares (CNIC), Madrid 28029, Spain
1 USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA
7 Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA; E-Mail: strak001@umn.edu
10 Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, AL 35294, USA; E-Mail: arnett@uab.edu
4 Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA; E-Mails: chao.lai@tufts.edu (C.Q.L.); jordov01@tufts.edu (J.M.O.)
8 Department of Laboratory Medicine and Pathology, University of Minnesota, MN55455, USA; E-Mail: tsaix001@umn.edu
2 Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA; E-Mails: mwojczyn@dsgmail.wustl.edu (M.K.W.); iborec
AuthorAffiliation_xml – name: 10 Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, AL 35294, USA; E-Mail: arnett@uab.edu
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Snippet Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein...
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StartPage 536
SubjectTerms candidate gene study
fenofibrate
genetic risk score
GOLDN
HDL size
LDL size
lipoprotein
NMR
particle size
pharmacogenetics
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Title Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate
URI https://www.ncbi.nlm.nih.gov/pubmed/25157911
https://search.proquest.com/docview/1558521552
https://pubmed.ncbi.nlm.nih.gov/PMC4192626
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Volume 3
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