Polymorphisms in the CRP Gene and Cardiovascular Events

To the Editor: In their study of polymorphisms in the C-reactive protein (CRP) gene, Dr Lange and colleagues1 found that genetic variation in the CRP gene was associated with CRP levels and that genetic variants were differentially associated with cardiovascular disease (CVD) events in white and black participants. The authors base their hypothesis on an analogous earlier study showing that the association of a PSSK9 variant with both low-density lipoprotein cholesterol (LDL-C) and CVD suggested that lifelong reduction in LDL-C would reduce CVD. The likely effect of treatments targeting modifiable risk factors for CVD depends on robust causal inference of the risk factor–disease relationship, which is aided by mendelian randomization methods. Because these methods involve formally combining the CRP gene and gene-disease associations,2 it is disappointing that Lange et al did not use their results to provide an estimate of the causal effect of CRP on CVD risk for . . .