Suk Danik J, Chasman D I, Cannon C P, Miller D T, Zee R Y L, Kozlowski P, Kwiatkowski D J, Ridker P M
The Donald W Reynolds Center for Cardiovascular Research, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02115, USA.
Ann Hum Genet. 2006 Nov;70(Pt 6):705-16. doi: 10.1111/j.1469-1809.2006.00272.x.
The aim of this research was to assess whether common genetic variants within the C-reactive protein gene (CRP) are related to the degree of acute rise in plasma C-reactive protein (CRP) levels following an acute coronary syndrome (ACS). While polymorphisms within CRP are associated with basal CRP levels in healthy men and women, less is known about the relationship of such genetic variants and the degree of CRP rise during and after acute ischemia. Plasma CRP is associated with increased rates of recurrent coronary events. We evaluated seven common genetic variants within CRP and assessed their relationship to the degree of rise in CRP levels immediately following an acute coronary syndrome in 1827 European American patients. Variants in the putative promoter region, -757T > C and -286C > T > A, were associated with the highest CRP elevations after ACS. Patients with two copies of the A allele of SNP -286C > T > A had median CRP values of 76.6 mg/L, compared to 11.1 mg/L in patients with no copies of the rare variant (p-value <0.0001), post ACS. The lowest CRP values were found for patients with minor alleles of the exonic 1059G > C and the 3'untranslated region 1846G > A SNPs. For example, patients homozygous for the minor allele of 1059G > C had 71% lower median CRP values than those homozygous for the major allele [3.5 vs 12.0 mg/L, p < 0.0001]. These trends persisted in the chronic stable phase after ischemia had resolved, and after adjustment for infarct size by peak creatinine kinase levels and clinical status by Killip class. Assessment of CRP genetic variants identified patients with higher and lower CRP elevation after acute coronary syndrome.
本研究的目的是评估C反应蛋白基因（CRP）内的常见基因变异是否与急性冠状动脉综合征（ACS）后血浆C反应蛋白（CRP）水平的急性升高程度相关。虽然CRP内的多态性与健康男性和女性的基础CRP水平相关，但对于此类基因变异与急性缺血期间及之后CRP升高程度之间的关系，人们了解较少。血浆CRP与复发性冠状动脉事件的发生率增加相关。我们评估了CRP内的7种常见基因变异，并在1827名欧美患者中评估了它们与急性冠状动脉综合征后即刻CRP水平升高程度的关系。假定启动子区域的变异-757T>C和-286C>T>A与ACS后最高的CRP升高相关。SNP -286C>T>A的A等位基因有两个拷贝的患者，ACS后CRP中位数为76.6mg/L，而没有该罕见变异拷贝的患者为11.1mg/L（p值<0.0001）。外显子1059G>C和3'非翻译区1846G>A SNP的次要等位基因的患者CRP值最低。例如，1059G>C次要等位基因纯合的患者，其CRP中位数比主要等位基因纯合的患者低71%[3.5对12.0mg/L，p<0.0001]。这些趋势在缺血缓解后的慢性稳定期持续存在，并且在通过峰值肌酸激酶水平调整梗死面积和通过Killip分级调整临床状态后仍然存在。对CRP基因变异的评估确定了急性冠状动脉综合征后CRP升高较高和较低的患者。
