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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MDPI AG
2014-08-01
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| Series: | Biology |
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| Online Access: | http://www.mdpi.com/2079-7737/3/3/536 |
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| author | Alexis C. Frazier-Wood Mary K. Wojczynski Ingrid B. Borecki Paul N. Hopkins Chao-Qiang Lai Jose M. Ordovas Robert J. Straka Micheal Y. Tsai Hemant K. Tiwari Donna K. Arnett |
| author_facet | Alexis C. Frazier-Wood Mary K. Wojczynski Ingrid B. Borecki Paul N. Hopkins Chao-Qiang Lai Jose M. Ordovas Robert J. Straka Micheal Y. Tsai Hemant K. Tiwari Donna K. Arnett |
| author_sort | Alexis C. Frazier-Wood |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T19:52:11Z |
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| publishDate | 2014-08-01 |
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| spelling | doaj.art-92b791fb2fe04b27b440e7ad9c6159a92023-08-02T03:08:04ZengMDPI AGBiology2079-77372014-08-013353655010.3390/biology3030536biology3030536Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to FenofibrateAlexis C. Frazier-Wood0Mary K. Wojczynski1Ingrid B. Borecki2Paul N. Hopkins3Chao-Qiang Lai4Jose M. Ordovas5Robert J. Straka6Micheal Y. Tsai7Hemant K. Tiwari8Donna K. Arnett9USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USADepartment of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USANutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USANutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USADepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USADepartment of Laboratory Medicine and Pathology, University of Minnesota, MN55455, USASection on Statistical Genetics, University of Alabama at Birmingham, School of Public Health, AL 35294, USADepartment of Epidemiology, University of Alabama at Birmingham, School of Public Health, AL 35294, USALipoprotein 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.http://www.mdpi.com/2079-7737/3/3/536pharmacogeneticscandidate gene studylipoproteinfenofibrateNMRGOLDNgenetic risk scoreparticle sizeLDL sizeHDL size |
| spellingShingle | Alexis C. Frazier-Wood Mary K. Wojczynski Ingrid B. Borecki Paul N. Hopkins Chao-Qiang Lai Jose M. Ordovas Robert J. Straka Micheal Y. Tsai Hemant K. Tiwari Donna K. Arnett Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate Biology pharmacogenetics candidate gene study lipoprotein fenofibrate NMR GOLDN genetic risk score particle size LDL size HDL size |
| title | Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate |
| title_full | Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate |
| title_fullStr | Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate |
| title_full_unstemmed | Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate |
| title_short | Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate |
| title_sort | genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate |
| topic | pharmacogenetics candidate gene study lipoprotein fenofibrate NMR GOLDN genetic risk score particle size LDL size HDL size |
| url | http://www.mdpi.com/2079-7737/3/3/536 |
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