Association of common C-Reactive Protein (CRP) gene polymorphisms with baseline plasma CRP levels and fenofibrate response - The GOLDN Study
Association of common C-Reactive Protein (CRP) gene polymorphisms with baseline plasma CRP levels and fenofibrate response - The GOLDN Study
复制标题
DOI：
10.2337/dc07-1687
复制
发表时间：
2008-05-01
期刊：
影响因子：
16.2
通讯作者：
Ordovas, Jose M.
中科院分区：
文献类型：
--
作者：
Shen, Jian;Arnett, Donna K.;Ordovas, Jose M.
目的-C反应蛋白（CRP）是一种炎症标志物，有助于预测心血管疾病。我们研究了CRP多态性对基线CRP水平和非诺贝特诱导的代谢综合征受试者CRP变化的影响。（m772 A> G，m301 G> A > T，i178 T> A，3u 1273 C> T和3u 2131 C> T），基线血浆CRP水平在1，123名白色美国参与者参与了降脂药物遗传学和饮食网络（GOLDN）研究，并研究了这些SNP对CRP反应的调节作用。对290名患有代谢综合征的参与者进行了为期一周的非诺贝特治疗。结果-m301 G> A > T存在强相关性（rs3091244; P = 0.003）、i178 T> A（rs 1417938，P = 0.001）、3u 1273 C> T（rs 1130864; P = 0.001）和3u 2131 C> T（rs 1205; P < 0.001）与基线CRP水平。此外，在患有代谢综合征的受试者中，与TA和AA受试者相比，非诺贝特诱导i178 T> A的TT受试者的CRP水平降低最大（TT为-30，TA为-19，AA为-11%; P = 0.004）。类似地，对于m301 G> A > T，主要等位基因携带者显示CRP比非携带者降低最大（GG为-20，GA和GT为-15，TA和AA为-0.3%，P = 0.020）。我们的研究结果表明，CRP基因内的常见遗传变异影响基线CRP水平，并进一步调节代谢综合征受试者的CRP反应，非诺贝特这些知识有助于更好地预测治疗成功。
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.RSEARCH DESIGN AND 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.