title: The anti-inflammatory CASPASE-12 gene does not influence SLE phenotype in African-Americans.
abstract: 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.
authors.affiliation: Public Health Program, College of Education and Health Sciences, Touro University, CA, United States.
authors.forename: Trista
authors.initials: T
authors.lastname: Fuchs
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
authors.affiliation: Program in Medical Health Sciences, College of Osteopathic Medicine, Touro University, CA, United States; Department of Basic Sciences, College of Osteopathic Medicine, Touro University, CA, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Simon
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Sivils
authors.affiliation: Program in Medical Health Sciences, College of Osteopathic Medicine, Touro University, CA, United States; Department of Basic Sciences, College of Osteopathic Medicine, Touro University, CA, United States. Electronic address: evan.hermel@tu.edu.
authors.forename: Evan
authors.initials: E
authors.lastname: Hermel
mesh_terms: D000328:Adult; D001741:Black or African American; D000483:Alleles; D000974:Antibodies, Antinuclear / Q000097:blood; D053454:Caspase 12 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000235:genetics*
chemical_list: D000974:Antibodies, Antinuclear; D053583:Interleukin-1beta; D053454:Caspase 12
keywords: Autoimmunity; CASPASE-12; Genetics; Inflammation; Interleukin-1; Lupus