A functional polymorphism of Toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease

Human Toll-like receptor 4 (TLR4) transduces proinflammatory cytokine relea se by human cells in response to lipopolysaccharide (LPS). This study teste d the hypothesis that, if TLR4 is rate limiting for a successful response t o bacterial LPS in humans, a human gene polymorphism that results in the am ino acid substitution Asp299Gly and causes reduced expression and function of TLR4 should influence susceptibility to or severity of natural gramnegat ive infection. The allele frequency of the Asp299Gly polymorphism was 5.9% among 879 blood donors, 6.5% among 1047 patients with microbiologically pro ven meningococcal disease, and 4.1% among 86 patients who died of meningoco ccal disease. No significant differences were observed, including those ana lyzed after stratification of the infected population by age and by meningo coccal serogroup. Therefore, this functional TLR4 polymorphism does not inf luence susceptibility to or severity of meningococcal disease.