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Association of common C-reactive protein (CRP) gene polymorphisms with baseline plasma CRP levels and fenofibrate response: The GOLDN Study

¹Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
²Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL
³Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN
⁴Human Genetics Center, University of Texas, Houston, TX
⁵Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
⁶Division of Statistical Genomics, Washington University in Saint Louis, School of Medicine, Saint Louis, MO
⁷Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN

jose.ordovas{at}tufts.edu

ABSTRACT

Objective: C-reactive protein (CRP) is an inflammatory marker that contributes to the prediction of cardiovascular diseases (CVD). We investigated the influences of CRP polymorphisms on baseline CRP levels and fenofibrate-induced CRP changes in subjects with the metabolic syndrome (MetS).

RESEARCH DESIGN AND METHODS: We examined the association of CRP single nucleotide polymorphisms (SNPs) (m772A>G, m301G>A >T, i178T>A, 3u1273C>T, 3u2131C>T) with baseline plasma CRP levels among 1123 US White participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, and the modulating effect of these SNPs on CRP response to a 3-week fenofibrate treatment among 290 participants with the MetS.

Results: There were strong associations of m301G>A>T (rs3091244, P=0.003), i178T>A (rs1417938, P=0.001), 3u1273C>T (rs1130864, P=0.001) and 3u2131C>T (rs1205, P<0.001) with baseline CRP levels. Moreover, among MetS subjects fenofibrate induced the greatest reduction in CRP levels for TT subjects of the i178T>A compared to TA and AA subjects (–30% for TT, –19% for TA, –11% for AA, P=0.004). Similarly, for the m301G>A>T, major allele carriers displayed maximal reduction of CRP over non-carriers (–20% for GG, –15% for GA and GT, –0.3% for TA and AA, P=0.02).

Conclusions: Our results demonstrate that common genetic variants within the CRP gene affect baseline CRP levels and further modulate CRP response in subjects with the MetS treated with fenofibrate. This knowledge could contribute to a better prediction of therapeutic success.

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