Abstract P3010: The C10X Polymorphism In The CARD8 Gene Is Associated With The Levels Of CCL20 And IL-6 Proteins In Healthy Young Men

Abstract

Introduction: The Caspase Activation and Recruitment Domain 8 (CARD8) protein is a component of innate immunity which has been associated with regulation of proteins involved in inflammation. We have previously identified CARD8 to act as a regulator of cytokines and chemokines in atherosclerotic lesions, and via knockdown of CARD8 in human umbilical vein endothelial cells (HUVECs). Aim: The present study examines the role of the genetic variation rs2043211 in the CARD8 gene (encoding C10X variant) in relation to a selection of markers of inflammation (Olink inflammation panel; https://olink.com). The CARD8 polymorphism is assumed to mimic the knockdown of CARD8. Methods: DNA was extracted from blood samples from 233 Swedish young healthy men (aged 18.0-25.9 years), collected in the Lifestyle, Biomarkers and Atherosclerosis (LBA) cohort, Örebro University, Sweden. Genotyping of the CARD8 polymorphism was performed with TaqMan real time PCR on DNA from blood samples from young healthy men ( n =233). Protein levels across genotypes were analyzed by additive model (TT vs TA vs AA) by analysis of variance (ANOVA). The recessive (TT + TA vs AA) and dominant (TT vs TA + AA) models were analyzed by t-test. Results: The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6. The dominant model resulted in p= 0.023 and p= 0.037 for CCL20 and IL-6, respectively. The association remained significant also after adjustment for age and potential intermediate variables (Body Mass Index, low density lipoprotein cholesterol, triglycerides, insulin, and systolic blood pressure). The results agree with previous observations in other cell types. Conclusions: We have shown an association between the polymorphism rs2043211 encoding a truncated variant of the CARD8 gene and lower levels of CCL20 and IL-6 levels in men. Our data indicate that CARD8 may be involved in the regulation of these proteins. Additional in vitro studies are needed to reveal the functional mechanistic effects of the polymorphism. Future longitudinal studies of the polymorphism are warranted to elucidate the clinical effect of these proteins.