Impact of genetic and environmental factors on hsCRP concentrations and response to therapeutic agents.
BACKGROUND
Inflammation plays an instrumental role in all stages of atherosclerosis. High-sensitivity C-reactive protein (hsCRP), a systemic inflammatory marker, has been gaining recognition as an independent risk factor for cardiovascular disease (CVD). Both baseline hsCRP concentrations and drug-induced hsCRP changes are highly variable and potentially subject to genetic regulation.


BACKGROUND
This review summarizes the current studies examining the effect of genetic and environmental factors on baseline plasma hsCRP concentrations, with a main focus on C-reactive protein, pentraxin-related (CRP) genetic polymorphisms and various dietary components that affect hsCRP concentrations. We also address the association of CRP genetic variations with CVD risk, a relationship that may support or refute the causality of CRP in the atherosclerotic process. Moreover, we discuss the impact of CRP genetic polymorphisms on hsCRP changes in response to 3-week fenofibrate treatment in the genetic intervention of the Genetics of Lipid Lowering Drugs and Diet Network study.


CONCLUSIONS
Genetic variants on the CRP locus and other loci and dietary and lifestyle factors are responsible for the interindividual variability of plasma hsCRP concentrations. CRP genetic variants further influence differing plasma hsCRP response after 3-week fenofibrate treatment in patients with metabolic syndrome. Future studies focusing on the influence and interaction of genetic variation on the hsCRP response to dietary and other behavior modification as well as drug treatment could have important implications for the development of more personalized preventive and therapeutic approaches to reduce CVD.
Shen
Jian
J
Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
Ordovas
Jose M
JM
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D004032:Diet; D011345:Fenofibrate / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008019:Life Style; D008055:Lipids / Q000097:blood; D011110:Polymorphism, Genetic; D012307:Risk Factors
D015415:Biomarkers; D000960:Hypolipidemic Agents; D008055:Lipids; D002097:C-Reactive Protein; D011345:Fenofibrate