Association of common C-reactive protein (CRP) gene polymorphisms with baseline plasma CRP levels and fenofibrate response: the GOLDN study.
OBJECTIVE
C-reactive protein (CRP) is an inflammatory marker that contributes to the prediction of cardiovascular disease. We investigated the influences of CRP polymorphisms on baseline CRP levels and fenofibrate-induced CRP changes in subjects with the metabolic syndrome.


METHODS
We examined the association of CRP single nucleotide polymorphisms (SNPs) (m772A>G, m301G>A >T, i178T>A, 3u1273C>T, and 3u2131C>T) with baseline plasma CRP levels among 1,123 white U.S. 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 metabolic syndrome.


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 subjects with the metabolic syndrome, fenofibrate induced the greatest reduction in CRP levels for TT subjects of the i178T>A compared with TA and AA subjects (-30 for TT, -19 for TA, and -11% for AA; P = 0.004). Similarly, for the m301G>A>T, major allele carriers displayed maximal reduction of CRP over noncarriers (-20 for GG, -15 for GA and GT, and -0.3% for TA and AA; P = 0.020).


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 metabolic syndrome treated with fenofibrate. This knowledge could contribute to a better prediction of therapeutic success.
Shen
Jian
J
Nutrition and Genomics Laboratory, Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111-1524, USA.
Arnett
Donna K
DK
Parnell
Laurence D
LD
Peacock
James M
JM
Lai
Chao-Qiang
CQ
Hixson
James E
JE
Tsai
Michael Y
MY
Province
Michael A
MA
Straka
Robert J
RJ
Ordovas
Jose M
JM
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D002097:C-Reactive Protein; D004247:DNA; D011345:Fenofibrate