Author`s Reply.

To the Editor,

We would like to thank the authors of the letter for the comments on our recently published study (1) and for showing interest in our study and putting forward some important points. Genetic polymorphism may be attributed to different ethnic populations or etiology (2, 3). Therefore, the subgroups were analyzed by ethnicity and etiology in our study (Fig. ) (1). The limitations of our article mentioned “different disease statuses may have influenced the data explanation of the included studies”. However, only two subgroups (myocardial infarction and others) were present based on the etiology because the relationship between caspase recruitment domain-containing protein 8 (CARD8) and cardiovascular disease is not fully investigated and understood. Additionally, because Asian and Caucasian populations comprised the ethnicity group in our study, the ethnicity subgroups of these two populations were analyzed. Therefore, further studies with diverse populations and etiologies are needed to explore the association between CARD8 and cardiovascular disease susceptibility. Potential gene polymorphisms for cardivascular disease have been reported rampantly. Indeed, focus on the interaction between the CARD8 rs2043211 polymorphism and the NLR pyrin domain containing 3 (NLRP3) gene polymorphism has been increasing (4); however, the interactions between the CARD8 rs2043211 polymorphism and other gene polymorphisms have not been completely analyzed although the the NLR pyrin domain containing 1 (NLRP1) rs2670660 single-nucleotide polymorphism SNP and the NLRP1 rs12150220–rs2670660 A-G haplotype are associated (4, 5). Because the article concluded that “the exact mechanism by which the CARD8 rs2043211 gene polymorphism influences cardiovascular diseases susceptibility remains to be elucidated,” further research is necessary. Finally, the results of the molecular weight and genetic content analyses are concordant with our study and provide another explanation.