Caspase recruitment domain-containing protein 8 rs2043211 polymorphism and cardiovascular disease susceptibility

We read the publication on “Association between caspase recruitment domain-containing protein 8 rs2043211 polymorphism (CARD8) and cardiovascular disease susceptibility: A systematic review and meta-analysis” with great interest (1). Huang et al. (1) concluded that “CARD8 rs2043211 polymorphism is associated with cardiovascular diseases”. There are some concerns with respect to this report. Firstly, the additional effect of ethnic differences should be studied. Secondly, a subgroup analysis should be performed for each cardiovascular disease. Different cardiovascular diseases have different underlying pathophysiological processes, and the effects of underlying genetic polymorphisms may be different. Also, the effect of other concurrent genetic polymorphisms should be mentioned. Along with CARD8 polymorphism, other polymorphisms can affect cardiovascular disease susceptibility. Finally, we tried to analyze and calculate for the difference of molecular weight, using the same technique described in previous publications (2, 3), in cases of different polymorphisms of CARD8. Comparing AT genotypes to AA genotypes, the molecular difference at the corresponding site is 141.1/ mol (393.3/mol versus 534.4/mol). This implies that more amount of CARD8 genetic content is required for the processing of the final protein in the AA genotype. This may imply less involvement of CARD8 in the inflammation process, which is further related to the pathogenesis of cardiovascular diseases, in case of the CARD8 AT genotype. This is an additional explanation to the findings of the meta-analysis by Huang et al. (1)