CARD8 polymorphisms among bacterial meningitis patients in North-West Ethiopia

Abstract Background The severity of infectious disease outcomes is believed to depend on the virulence factors of the pathogen in combination with individuals’ unique immune response. CARD8 has been suggested to act as a regulator of the NLRP3 inflammasome, a major regulator of the innate immune proinflammatory response, and has been suggested to modulate the host response to common inflammatory diseases. In the present study, the C10X genetic polymorphism in the CARD8 gene was investigated in relation to bacterial meningitis. Methods A total of 400 clinically suspected meningitis patients hospitalized at the University of Gondar Comprehensive specialized Hospital were enrolled in the study. Cerebrospinal fluid (CSF) and blood samples were collected from all enrolled patients for laboratory investigations. The collected CSF was cultured, and all the results obtained from the culture were confirmed using direct RT‒PCR. Genotyping of whole-blood samples was performed for CARD8 gene using a TaqMan assay. The results were compared with apparently healthy controls and with PCR-negative meningitis suspected patients. Results Of the included patients, 57% were men and the most common clinical signs and symptoms were fever (81%), headache (80%), neck stiffness (76%), nausea (68%), and vomiting (67%). Microbiology culture identified seven patients with bacterial meningitis caused by Neisseria meningitidis (n = 4) and Streptococcus pneumoniae (n = 3). The RT-PCR revealed 39 positive samples for N. meningitidis (n = 10) and S. pneumoniae (n = 29). A total of 332 whole-blood samples were genotyped, with the following results: 151 (45.5%) C10X heterozygotes, 59 (17.7%) C10X homozygotes and 122 (36.7%) wild-type genotypes. The presence of the C10X polymorphism in the CARD8 gene was more prevalent in suspected meningitis patients than in healthy controls (OR 1.2; 1.00-1.5). Homozygote C10X polymorphic gene carriers were more susceptible to infectious disease. The presence of viable or active bacterial infection was found to be associated with the presence of heterozygous C10X carriers. Conclusions A greater proportion of C10X in the CARD8 gene in confirmed bacterial meningitis patients and clinically diagnosed meningitis patients than in healthy controls. Homozygote C10X polymorphic gene carriers were more susceptible to infectious disease than were heterozygote gene carriers and healthy controls.