Complement component C6 is a part of the
membrane attack complex that forms a pore-like structure in cell membranes following complement activation. Deficiency of terminal
complement components including C6 predisposes individuals to
infection with Neisseriae. Using polymerase chain reaction/single-strand conformation polymorphism analysis followed by
DNA sequencing, we screened genomic
DNA from 200 randomly chosen blacks and an equal number from whites for three loss-of-function C6 mutations. Ten blacks and two whites were found to be heterozygous for one of the mutations. Two of the mutations, 1195delC and 1936delG, were found exclusively in black individuals. A third previously undescribed mutation, 878delA, was found at equal frequency among the two groups. The difference between the two groups was significant (P = 0.027), indicating that
C6 deficiency due to these three mutations is more common among blacks than whites in the local area, principally Jefferson County, Alabama. In addition, three previously undescribed point mutations, two of which result in amino acid substitutions, were identified within exon 6. A review of the county health department records over the past 6 years revealed a higher incidence of
meningococcal meningitis in blacks due to serogroups Y and W-135 which paralleled the difference in the estimated prevalence of
C6 deficiency. Among black residents of the county (n = 235 598) there were 15 cases of
meningitis due to these two serogroups, compared with two cases in the white population (n = 422 604) (P = 0.002). We conclude that
C6 deficiency is more common among blacks than whites in the south-eastern United States, with a frequency approaching 1 in 1600 black individuals.