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Association between C10X polymorphism in the CARD8 gene and inflammatory markers in young healthy individuals in the
Karin Fransén1, Ayako Hiyoshi2, Geena V Paramel3
1Cardiovascular Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. Karin.h.franzen@oru.se.
Insights
The Caspase activation and recruitment domain 8 (CARD8) gene variant rs2043211 is linked to reduced CCL20 and IL-6 inflammatory markers in men. This study highlights CARD8
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Caspase activation and recruitment domain 8 (CARD8) is an innate immunity protein regulating NF-κB and inflammation.
- CARD8 expression is found in atherosclerotic lesions; a variant (rs2043211) correlates with lower inflammatory markers in myocardial infarction patients.
- This study investigates the role of CARD8 genetic variation in inflammation markers.
Purpose of the Study:
- To examine the association between the CARD8 rs2043211 polymorphism and inflammation markers in healthy young adults.
- To investigate potential sex-specific differences in these associations.
Main Methods:
- A cross-sectional study of 744 healthy individuals (18.0-25.9 years).
- Genotyping of CARD8 C10X (rs2043211) using TaqMan real-time PCR.
- Protein levels of inflammatory markers measured using the Olink inflammation panel.
- Linear models analyzed associations in men and women (separately for oral contraceptive users and non-users), considering additive, recessive, and dominant genetic models.
Main Results:
- The minor allele (A) of rs2043211 in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men.
- These associations remained significant after adjusting for age and potential intermediate variables.
- No significant association was observed in women.
Conclusions:
- CARD8 genetic variation may regulate CCL20 and IL-6 levels in men, supporting in vitro findings.
- The study highlights CARD8's role in inflammatory protein regulation.
- Further research is needed to clarify sex-specific differences and the potential influence of estrogen on inflammatory responses.
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.
