CASPASE-12 (CASP12) has a down-regulatory function during infection, and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal-Wallis non-parametric ANOVA with Mann-Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA patients.
CASPASE-12 (CASP12) modulates inflammation due to its ability to down-regulate inflammatory cytokines, particularly interleukin-1. Most humans possess the inactive pseudogene allele (CASP12p1) but a functional, non-truncated CASP12 allele [single nucleotide polymorphism #rs497116; A->G; ter124R] is found in 20% of persons of African descent. CASP12 is a risk factor for sepsis in persons of African descent. Rheumatoid arthritis (RA) is a serious and complex autoimmune disease that involves significant joint inflammation and destruction, and interleukin-1 contributes to the pathogenesis of RA. To determine if CASP12 may be protective against RA due to its anti-inflammatory functions, we genotyped 742 patients with rheumatoid arthritis and 342 controls from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis and the Veterans Affairs Rheumatoid Arthritis registries. Of RA patients, 17 (2.29%) were homozygous for CASP12, 146 (19.7%) were heterozygous, and 579 (78%) were homozygous for CASP12p1. These numbers did not vary significantly from controls. No significant differences were observed for CASP12 genotype on age of disease onset, seropositivity for rheumatoid factor or anti-CCP, baseline joint erosion, joint space narrowing scores, overall disease scores, C-reactive protein levels or erythrocyte sedimentation rates. Thus, CASP12 does not protect against RA in African-American patients, nor mitigates disease parameters.
education centered on the social determinants of health for both Ugandan and international health professional students-engages the contentious topic through structured intercultural dialogue. The methodology utilized provides Ugandan and international students alike the opportunity to not only examine the neglected and controversial global health issue but to develop the critical ability to constructively dialogue. Structure/Method/Design: SocMed's intercultural dialogue on sexual orientation aims to challenge students to engage in effective communication and develop an attitude and skill-set associated with inquiry rather than one that reinforces ideologies. SocMed utilizes Freirian pedagogy to create an innovative learning environment in which students participate as both learners and teachers to advance understanding of social determinants of health, social experience of illness, effective models for intervention, and applicable models for health advocacy. To discuss sexual orientation, SocMed utilizes a structured intercultural dialogue process, in which students develop skills of activelistening, inquiry, social analysis, and respectful articulation of personal beliefs. After defining terms and soliciting anonymous questions, students are broken into small groups with diverse representation. A series of questions are provided that prompt students to reflect on their own experiences of marginalization, their own socialization to sexual orientation, and health-related concerns of LGBTQ persons. Furthermore, in small groups, students are given the text of recent Ugandan legislation on the topic and are asked to read it, discuss it, and explore explanations for why the bill was introduced in Uganda. Outcomes & Evaluation: To gauge the impact of the sexual orientation dialogue along with other sessions taught in the 4-week immersion course, a formal self-assessment evaluation tool is utilized at the end of the course. Seventy-nine percent of the students stated that they "agreed" or "strongly agreed" that they found the [sexual orientation] section of the course interesting and [they] learned a considerable amount. Given the polarizing indications of students prior to the session, this represents significant impact. Furthermore, ethnographic observation indicates that students continue to effectively dialogue on sexual orientation outside of class. Going Forward: Creating safe spaces of trust and mutuality are central in SocMed's evolution; it is an essential dimension for sensitive dialogue to be fruitful. An ongoing challenge is SocMed's capacity to measure the impact of the dialogue on students and on their communities to which they return after the course. Funding: None.
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.
CASPASE-12 (CASP12) modulates inflammation by down-regulating inflammatory cytokines. CASP12 is a risk factor for sepsis in persons of African ancestry, as the functional CASP12 allele is present in about 20% of persons of African descent. Nearly all other human populations lack a functional CASP12 gene. Systemic lupus erythematosus (SLE) is a serious and complex autoimmune disease affecting multiple organ systems and is most common in African-American (AA) women. To determine if CASP12 may be protective against SLE, 596 AA SLE patients and 296 healthy controls from the Lupus Family Registry and Repository were genotyped for CASP12. Serum from 30 patients and controls was assayed by antibody arrays for 23 inflammatory cytokines and chemokines. There was a significant association between CASP12 and protection against serositis. CASP12 homozygosity was seen only in controls, and CASP12 was only in female, but not male patients without serositis compared to those with serositis. In male patients, CASP12 was protective against the development of arthritis. Expression of the Mig chemokine was statistically different between patients and controls, independent of genotype. No influence of CASP12 genotype was seen upon serum cytokine levels in patients vs controls. The results indicate that CASP12 is protective against lupus serositis and arthritis in AA patients, with possible gender influences for both. In addition, chemokines may contribute to the pathogenesis of SLE.
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