The Association between Polymorphism of CARD8 rs2043211 and Susceptibility to Arteriosclerosis Obliterans in Chinese Han Male Population

Abstract

Background and aims: Cholesterol crystals have been shown to cause inflammation. As a response to cholesterol crystal accumulation, the NLRP3 inflammasome is activated to produce IL-1β which eventually leads to atherosclerotic lesions. As a part of innate immunity, CARD8 is involved in the modulation of above mentioned inflammatory activities. The primary objective of this study was to investigate the association between polymorphism of CARD8 rs2043211 and susceptibility to arteriosclerosis obliterans (ASO) in Chinese Han male population. Methods: 758 male arteriosclerosis obliterans patients and 793 male controls were genotyped for rs2043211 with the TaqMan allele assays. Fasting blood-glucose (FBG), total cholesterol (TC), triglycerides (TG), urea nitrogen, creatinine, Serum uric acid, high density lipoprotein, low density lipoprotein, ALT, AST, and IL-1β in the blood were detected for all subjects. Clinical data were recorded to analyze the genotype-phenotype. Independent samples t-test was used to perform the comparisons between two groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to measure the strength of relationship in the genotype distribution and allele frequencies between patients and controls. The analysis of variance was used for a genotype-phenotype analysis of the ASO patients. Results: The genotypic and allelic frequencies in the ASO group were significantly different from that in the control group (P = 0.014 by genotype, P = 0.003 by allele). Those carrying the genotype TT had a higher risk for ASO than those carrying the genotype AA (OR = 1.494, 95%CI1.131-1.974, P = 0.005).The difference was also significant after the adjustment for the history of smoking, TC, LDL, fasting blood glucose, systolic blood pressure and BMI(OR = 1.525, 95%CI1.158-2.009, P = 0.003). Conclusion: Our finding suggests that the polymorphism of CARD8 rs2043211 is probably associated with the development of ASO in Chinese Han male population.

ANRILas a genetic marker for cardiovascular events in renal transplant patients - an observational follow-up cohort study

“…On the contrary, carriers of the minor T allele of the CARD8 SNP rs2043211 also displayed lower circulating C‐reactive protein and lower levels of the pro‐atherosclerotic chemokine MCP‐1 . Despite the fact that there are contradictory results regarding the risk allele for the CARD8 SNP rs2043211, our results are in concordance with other authors reporting the T allele as the risk allele.…”

“…The SNP rs2043211 of CARD8 changes cysteine to a premature termination codon, thus yielding a truncated protein, which influences the protein function . Previous investigations have studied the relationship of the CARD8 SNP with different inflammatory diseases including cardiovascular disease: myocardial infarction , coronary atherosclerosis and also with ischemic stroke . However, conclusions are confusing and renal transplant recipients have never been studied in this context.…”

The Genetic Polymorphisms of NLRP3 Inflammasome Associated with T Helper Cells in Patients with Multiple Myeloma

“…The SNP rs2043211 of CARD8 changes cysteine at codon10 to a premature termination codon, thus yielding a premature, truncated protein, which influences the protein function [38]. So far, more and more researches proved that the CARD8 SNP was associated with the increased risk of various cancers, such as nodular melanoma, hepatocellular carcinoma, and cervical cancer [38–40]. In our study, we found that the AT genotype of CARD8-C10X (rs2043211) was associated with the increased risk of MM.…”

Caspase recruitment domain-containing protein 8 (CARD8) rs2043211 polymorphism and cardiovascular disease susceptibility: a systematic review and meta-analysis

“…However, it was found to be associated with a lower expression of CARD8 in the plaque as well as with lower C-reactive protein and monocyte chemoattractant protein-1 levels in the plasma ( 8 , 15 , 16 ). However, in one Chinese cohort, rs2043211 was associated with ischemic stroke ( 10 ), and it is probably associated with the development of arteriosclerosis obliterans in the Chinese Han male population ( 11 ). Moreover, it has shown a modest protective effect against abdominal aortic aneurysms ( 24 ).…”

“…It is encoded by exon 13 in 19q13, and it changes cysteine to a premature termination codon at codon 10, thus influencing the protein’s function in inflammasome-mediated processes and nuclear factor (NF)-κB suppression ( 8 , 9 ). Statistics have shown that CARD8 polymorphisms are related to the CVD risk ( 10 ), but several studies have reported different conclusions ( 8 , 11 , 12 ). Here, we present the first meta-analysis verifying the association between SNP rs2043211 in the CARD8 gene and CVDs.…”