CASPASE-12 and rheumatoid arthritis in African-Americans

Marshall, Laura; Obaidullah, Mohammad; Fuchs, Trista; Fineberg, Naomi S.; Brinkley, Garland; Mikuls, Ted R.; Bridges, S. Louis; Hermel, Evan

doi:10.1007/s00251-014-0762-9

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…By contrast, another study found no correlation between caspase 12 variants and cytokine production 84 . There is some evidence to suggest that homozygosity for the full-length caspase 12 protein is linked to lower baseline joint narrowing scores in African-Americans with rheumatoid arthritis 86 . No association between a particular variant of caspase 12 and susceptibility to sepsis induced by the fungal pathogen Candida albicans and to community-acquired pneumonia was found 87, 88 .…”

Section: Enigmatic Roles Of Caspase 12mentioning

confidence: 99%

Converging roles of caspases in inflammasome activation, cell death and innate immunity

2015

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Inflammatory and apoptotic caspases are central players in inflammation and apoptosis, respectively. However, recent studies have revealed that these caspases have functions beyond their established roles. In addition to mediating cleavage of the inflammasome-associated cytokines interleukin-1β (IL-1β) and IL-18, inflammatory caspases modulate distinct forms of programmed cell death and coordinate cell-autonomous immunity and other fundamental cellular processes. Certain apoptotic caspases assemble structurally diverse and dynamic complexes to direct inflammasome and interferon (IFN) responses to fine tune inflammation. In this Review, we discuss the expanding and interconnected roles of caspases that highlight new aspects of this family of cysteine proteases in innate immunity.

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Section: Enigmatic Roles Of Caspase 12mentioning

confidence: 99%

Converging roles of caspases in inflammasome activation, cell death and innate immunity

2015

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“…This notion is supported by our observation that CASP12 genotype is not protective against the development of rheumatoid arthritis (RA) in AA, but is protective against RA radiologic abnormalities [34]. Surprisingly, obese African-American children had lower serum IL6 and Creactive protein levels, as well as less macrophage infiltration into adipose tissues, if they were CASP12-positive [35].…”

Section: Discussionmentioning

confidence: 86%

The anti-inflammatory CASPASE-12 gene does not influence SLE phenotype in African-Americans

et al. 2016

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In the vast majority of human populations, the gene encoding CASPASE-12 (CASP12) has a premature termination codon that precludes the production of protein. However, approximately 20% of persons of recent African descent have a single nucleotide polymorphism (#rs497116; A->G) that turns the stop codon into one encoding Arg. The subsequent functional allele is a risk factor for sepsis as it uniquely downregulates inflammatory cytokines in African-Americans (AA). To determine if CASP12 could be protective for systemic lupus erythematosus (SLE) in AA, we genotyped AA SLE patients and controls. There was a weak association between CASP12 genotype with the absence of anti-dsDNA autoantibodies in SLE patients. No effect was seen upon serum interleukin-1 beta levels, nor was any other protective effect noted for the CASP12 genotype, whether upon association with SLE, or any of the 11 American College of Rheumatology classification criteria. CASP12 genotype thus does not influence the phenotype of SLE in AA.

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“…CASP12, a cysteine protease [21], is widely expressed in 14 tissues such as the ovaries and endometrium and is highly correlated with members of the ICE subfamily [IL-1 invertase: IL-1β-converting enzyme (ICE)] that treats inflammatory cytokines [22,23]. In a study by Marshall et al [24], the expression of CASP12 was significantly down-regulated during an infection, and there are protective factors between its polymorphism and rheumatoid arthritis. Therefore, CASP12 role in inflammation is widely known [25]; however, there are currently few studies on CASP12 in cancers.…”

Section: Discussionmentioning

confidence: 99%

Analysis of CASP12 diagnostic and prognostic values in cervical cancer based on TCGA database

et al. 2019

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The present study aims to find a differential protein-coding gene caspase 12 (CASP12) in cervical cancer (CC) based on the (TCGA) database and verify its clinical diagnostic and prognostic values. The transcriptome and clinicopathological data of CC were downloaded from the TCGA database and through screening, we found that PDE2A and CASP12 were independent prognostic factors for CC patients. According to the median expression, the patients were divided into groups with high and low CASP12 and PDE2A expression. There was no difference in survival between PDE2A high and low expression groups (P=0.099), whereas there was a significant difference between CASP12 high and low expression groups (P=0.033). The serum from 68 CC patients (experimental group) and 50 healthy people (control group) was collected to detect the relative expression of CASP12 using qRT-PCR and plotted the ROC curve. The relative expression of CASP12 in the experimental group was significantly lower than in the control group (P<0.05). The area under the curve (AUC) of CASP12 was 0.865. There were statistically significant differences between CASP12 groups with high and low expression in terms of differentiation, lymph node metastasis, tumor size, FIGO staging, and clinical outcomes (P<0.05), but not in terms of age, HPV types and pathological types (P>0.05). The 3-year survival in the CASP12 low expression group was significantly worse than in the CASP12 high expression group (P=0.028). In conclusion, the expression level of CASP12 can be used as a diagnostic and prognostic biomarker for patients with CC.

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CASPASE-12 and rheumatoid arthritis in African-Americans

Cited by 5 publications

References 20 publications

Converging roles of caspases in inflammasome activation, cell death and innate immunity

Converging roles of caspases in inflammasome activation, cell death and innate immunity

The anti-inflammatory CASPASE-12 gene does not influence SLE phenotype in African-Americans

Analysis of CASP12 diagnostic and prognostic values in cervical cancer based on TCGA database

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