CARD8 rs2043211 Polymorphism is Associated with Gout in a Chinese Male Population

Abstract

Background &Aim: Previous studies have suggested genetic factors are involved in the development of gout. We performed a case-control study to investigate the genetic association between CARD8 rs2043211 polymorphism and gout. Methods: A total of 396 male patients with gout and 403 age- and sex- matched healthy controls were included in this study. Genotyping was performed using TaqMan SNP Genotyping Assays. An association analysis was carried out using the χ2 test. The genotype-phenotype analysis was also conducted. Results: The genotype distribution of CARD8 rs2043211 polymorphism confirmed to HWE in the controls (P = 0.27). There was an obvious difference in the genotype distribution of CARD8 rs2043211 polymorphism between cases and controls (P = 0.017). In addition, there was an obvious association between CARD8 rs2043211 polymorphism and gout under the recessive comparison model (AA vs. TT/TA: OR = 0.65, 95%CI 0.47-0.88, P = 0.006). Patients carrying genotype TT of CARD8 rs2043211 polymorphism had higher triglycerides levels compared to those carrying the AA genotype (2.77±2.08 mmol/L vs. 2.07±1.15 mmol/L, P = 0.01). Patients with the TT genotype also had significantly higher systolic blood pressure compared with those with the AA genotype (142.11±21.10 mmHg vs. 135.38±14.66 mmHg, P = 0.03). Patients carrying TT genotype also had an increased risk of renal calculus compared with those carrying the AA genotype. Conclusion: CARD8 rs2043211 polymorphism is significantly associated with susceptibility to gout in Chinese Han males.

Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study

“…This study identified that CARD8 rs2043211 was not associated with increased gout risk, which is in contrast to the known difference of genetic distribution of this SNP in the Chinese and European gout population (67). As far as we know, this study is the first to determine genetic association between the P2X7R SNP and gout patients, revealing that P2X7R polymorphism did not increase the risk of gout in our study population.…”

“…McKinney et al (7) demonstrated that the prevalence of CARD8 rs2043211 was different between gout and control patients in the European and Polynesian populations (OR 1.11, P = 0.023 and OR 1.15, P = 0.078, respectively). Another case-control study showed that the MAF (A allele) CARD8 gene was shown to have an increasing trend relative to the T allele in the Chinese male population (OR = 0.084, P = 0.08) (6). However, our study revealed no association of CARD8 rs2043211 with the presence of gout in Korean study population.…”

“…Although the precise pathogenic mechanism of gout has not been clearly determined, several crucial proteins such as the purinergic receptor P2X ligand-gated ion channel 7 ( P2X7R ) (345) and caspase activation and recruitment domain 8 ( CARD8 ) (67) proteins are known to be responsible for the pathogenesis of gout.…”

“…Genetic variants of CARD8 were identified to play a role in the pathogenesis of a variety of inflammatory diseases, such as rheumatoid arthritis (RA) (8) and inflammatory bowel disease (IBD) (9). Chen et al (6) demonstrated a significantly different genotypic distribution of the CARD8 rs2043211 polymorphism between gout and control patients in the Chinese population. Another candidate gene involved in gouty inflammation might be P2X7R , whose protein product binds with ATP and induces the efflux of K + ions through the P2X7R channel from cells, finally triggering activation of the NLRP3 inflammasome (34).…”

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

“…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 in inflammasome-mediated processes and NF-κB suppression [18,19]. Lots of studies show that the polymorphisms of CARD8 contribute to the development of some inflammatory diseases, such as inflammatory bowel disease [20][21][22], gout [23],abdominal aortic aneurysm [24], rheumatoid arthritis [17,25,26]and Alzheimer's disease [27,28]. As a part of innate immunity, CARD8 is involved in the modulation of inflammatory activities.…”