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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #224068
Title: Association of common C-protein (CRP) gene polymorphism with baseline plasma CRP levels and fenofibrate response: The GOLDN Study

Author
item SHEN, JIAN - JM USDA HNRCA @ TUFTS
item ARNETT, DONNA - UNIV OF ALABAMA
item Parnell, Laurence
item PEACOCK, JAMES - UNIV OF MINNESOTA
item Lai, Chao Qiang
item HIXSON, JAMES - UNIV OF TEXAS
item TSAI, MICHAEL - UNIV OF MINNESOTA
item PROVINCE, MICHAEL - WASHINGTON UNIVERSITY
item STRAKA, ROBERT - UNIV OF MINNESOTA
item Ordovas, Jose

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2008
Publication Date: 5/1/2008
Citation: Shen, J., Arnett, D.K., Parnell, L.D., Peacock, J.M., Lai, C., Hixson, J.E., Tsai, M.Y., Province, M., Straka, R.J., Ordovas, J.M. 2008. Association of common C-protein (CRP) gene polymorphism with baseline plasma CRP levels and fenofibrate response: The GOLDN Study. Diabetes Care. 31(5):910-915.

Interpretive Summary: C-reactive protein (CRP) is an inflammatory marker that contributes to the prediction of cardiovascular diseases (CVD). Plasma CRP levels are under genetic regulation. Fenofibrate is commonly used drug in the clinic for the management of dyslipidemia. Recent studies also suggest the anti-inflammatory effect of fenofibrate. In this study, we investigated the influence of genetic mutation (single nucleotide polymorphism, SNP) at CRP gene on baseline CRP levels and fenofibrate-induced CRP changes in subjects with the metabolic syndrome (MetS). CRP SNPs (m772A>G, m301G>A >T, i178T>A, 3u1273C>T, 3u2131C>T) were genotyped in 1123 US White participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. We observed strong associations of m301G>A>T , i178T>A , 3u1273C>T and 3u2131C>T with baseline CRP levels. Moreover, the i178T>A and m301G>A>T further modulated CRP responses to a 3-week fenofibrate treatment among MetS such that the wild type carriers had greater reduction of CRP compared to the non-wild type carriers for both SNPs. 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.

Technical Abstract: OBJECTIVE-C-reactive protein (CRP) is an inflammatory marker that contributes to the prediction of cardiovascular diseases (CVD). We investigated the influence 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 (-28% for GG, -42% for GT, -19% for GA, -14% for TA and -2% for 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.