BACKGROUND: The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression of CARD8 mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) of CARD8 has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in the CARD8 gene in relation to a selection of markers of inflammation.
METHODS: In a cross-sectional study of young healthy individuals (18.0-25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel ( https://olink.com/ ). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models.
RESULTS: The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables.
CONCLUSIONS: Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women. These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored.

The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.

BACKGROUND: Previous studies showed that postinfectious autoimmunity and immune deficiency played an important role in the pathogenesis of Tourette syndrome. CARD8 can suppress activity of NF-ΚB activated by inflammatory mediators.
OBJECTIVE: To study the association between the rs2043211 polymorphism in CARD8 and susceptibility to Tourette syndrome in Chinese Han population.
METHODS: We recruited 279 patients diagnosed with Tourette syndrome and their parents for the study. Genotyping for CARD8 rs2043211 single-nucleotide polymorphism was performed using predesigned TaqMan single-nucleotide polymorphism genotyping assay. The genetic contribution of this single-nucleotide polymorphism was evaluated using transmission disequilibrium test and haplotype relative risk and the haplotype-based haplotype relative risk.
RESULTS: The results of the allelic and genotypic distribution of rs2043211 polymorphism in CARD8 showed that both the Tourette syndrome patients group and the parents group are in Hardy-Weinberg equilibrium. No significant differences were observed in the mutant allele transmission (transmission disequilibrium test = 1.107, df = 1, p = 0.322). Results of haplotype relative risk analysis showed that no statistical significant difference was found in the genotypic frequency (AA/AT/TT) of Tourette syndrome patients passed from parents (haplotype relative risk = 1.152, χ(2 )= 0.494, p = 0.482, 95% CI = 0.777-1.708). Similarly, the analysis of haplotype-based haplotype relative risk was also not to support a statistically significant association in allelic frequency (A/T) of Tourette syndrome patients passed from parents (haplotype-based haplotype relative risk = 1.130, χ(2 )= 1.037, p = 0.308, 95% CI = 0.893-1.429).
CONCLUSIONS: Our results suggest CARD8 might not play a role in the pathogenesis of Tourette syndrome in Chinese Han population. However, the results still need to be tested in a larger sample and different populations.