Association between NLRP3 rs10754558 and CARD8 rs2043211 Variants and Susceptibility to Chronic Kidney Disease

Russa, Antonella La; Lofaro, Danilo; Montesanto, Alberto; Russa, Daniele La; Zaza, Gianluigi; Granata, Simona; Dio, M. Di; Serra, Raffaele; Andreucci, Michele; Bonofiglio, Renzo; Perri, Anna

doi:10.3390/ijms24044184

Cited by 3 publications

(1 citation statement)

References 63 publications

(74 reference statements)

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“…-Increased susceptibility to chronic kidney disease with or without NLRP3 rs10754558 [113]. -Increased susceptibility to psoriasis [114].…”

Section: Card8 Inhibits Inflammasome Activation and Pro-inflammatory ...mentioning

confidence: 99%

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

Karakaya,

Slaufova,

Di Filippo

et al. 2024

Cells

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Inflammasomes comprise a group of protein complexes with fundamental roles in the induction of inflammation. Upon sensing stress factors, their assembly induces the activation and release of the pro-inflammatory cytokines interleukin (IL)-1β and -18 and a lytic type of cell death, termed pyroptosis. Recently, CARD8 has joined the group of inflammasome sensors. The carboxy-terminal part of CARD8, consisting of a function-to-find-domain (FIIND) and a caspase activation and recruitment domain (CARD), resembles that of NLR family pyrin domain containing 1 (NLRP1), which is recognized as the main inflammasome sensor in human keratinocytes. The interaction with dipeptidyl peptidases 8 and 9 (DPP8/9) represents an activation checkpoint for both sensors. CARD8 and NLRP1 are activated by viral protease activity targeting their amino-terminal region. However, CARD8 also has some unique features compared to the established inflammasome sensors. Activation of CARD8 occurs independently of the inflammasome adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), leading mainly to pyroptosis rather than the activation and secretion of pro-inflammatory cytokines. CARD8 was also shown to have anti-inflammatory and anti-apoptotic activity. It interacts with, and inhibits, several proteins involved in inflammation and cell death, such as the inflammasome sensor NLRP3, CARD-containing proteins caspase-1 and -9, nucleotide-binding oligomerization domain containing 2 (NOD2), or nuclear factor kappa B (NF-κB). Single nucleotide polymorphisms (SNPs) of CARD8, some of them occurring at high frequencies, are associated with various inflammatory diseases. The molecular mechanisms underlying the different pro- and anti-inflammatory activities of CARD8 are incompletely understood. Alternative splicing leads to the generation of multiple CARD8 protein isoforms. Although the functional properties of these isoforms are poorly characterized, there is evidence that suggests isoform-specific roles. The characterization of the functions of these isoforms, together with their cell- and disease-specific expression, might be the key to a better understanding of CARD8’s different roles in inflammation and inflammatory diseases.

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“…-Increased susceptibility to chronic kidney disease with or without NLRP3 rs10754558 [113]. -Increased susceptibility to psoriasis [114].…”

Section: Card8 Inhibits Inflammasome Activation and Pro-inflammatory ...mentioning

confidence: 99%

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

Karakaya,

Slaufova,

Di Filippo

et al. 2024

Cells

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Aging and chronic kidney disease: epidemiology, therapy, management and the role of immunity

Tang,

Jiang,

Zhao

et al. 2024

Clinical Kidney Journal

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Chronic kidney disease (CKD) is now an unquestionable progressive condition that affects more than 10% of the general population worldwide, and has emerged as one of the most important causes of global mortality. It is clear that the prevalence of CKD among aging population is significantly elevated. It involves a board range of complex and poorly understood concerns in older adults such as frailty, malnutrition, sarcopenia, and even cognitive and mental dysfunction. In kidneys, renal function such as glomerular filtration, urine concentration and dilution, and homeostasis of sodium and potassium, can be influenced by the aging process. In addition, it's worth noting that CKD and end stage of kidney disease (ESRD) patients are often accompanied by an activation of immune system and inflammation. It involves both the innate and adaptive immune system. Based on these backgrounds, in this review article, we attempt to summarize the epidemiological characteristics of CKD in aging population, discuss the immunological mechanisms in aging-related CKD, and furnish the reader with the process in therapy and management for elderly patients with CKD.

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Chronic osteomyelitis risk is associated with NLRP3 gene rs10754558 polymorphism in a Chinese Han Population

Qu,

Jiang,

et al. 2024

BMC Med Genomics

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Background Single nucleotide polymorphisms (SNPs) in the nucleotide-binding domain leucine-rich repeat protein-3 (NLRP3) gene are reported to be linked to many inflammatory disorders. However, uncertainty persists over the associations between these SNPs and susceptibilities to chronic osteomyelitis (COM). This study aimed to investigate potential relationships between NLRP3 gene SNPs and the risks of developing COM in a Chinese Han cohort. Methods The four tag SNPs of the NLRP3 gene were genotyped in a total of 428 COM patients and 368 healthy controlsusing the SNapShot technique. The genotype distribution, mutant allele frequency, and the four genetic models (dominant, recessive, homozygous, and heterozygous) of the four SNPs were compared between the two groups. Results A significant association was found between rs10754558 polymorphism and the probability of COM occurence by the heterozygous model (P = 0.037, odds ratio [OR] = 1.541, 95% confidence interval [CI] = 1.025–2.319), indicating that rs10754558 may be associated with a higher risk of developing COM.In addition, possible relationship was found between rs7525979 polymorphism and the risk of COM development by the outcomes of homozygous (P = 0.073, OR = 0.453, 95% CI = 0.187–1.097) and recessive (P = 0.093, OR = 0.478, 95% CI = 0.198–1.151) models, though no statistical differences were obtained. Conclusions Outcomes of the present study showed, for the first time, that rs10754558 polymorphism of the NLRP3 gene may increase the risk of COM development in this Chinese Han population, with genotype CG as a risk factor. Nonetheless, this conclusion requires verification from further studies with a larger sample size.

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Association between NLRP3 rs10754558 and CARD8 rs2043211 Variants and Susceptibility to Chronic Kidney Disease

Cited by 3 publications

References 63 publications

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

Aging and chronic kidney disease: epidemiology, therapy, management and the role of immunity

Chronic osteomyelitis risk is associated with NLRP3 gene rs10754558 polymorphism in a Chinese Han Population

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