High prevalence of complement component C6 deficiency among African-Americans in the South-eastern USA

Complement component C6 is a part of the membrane attack complex that forms a pore-like structure in cell membranes following complement activation. D eficiency of terminal complement components including C6 predisposes indivi duals to infection with Neisseriae. Using polymerase chain reaction/single- strand conformation polymorphism analysis followed by DNA sequencing, we sc reened 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 mutation s, 1195delC and 1936delG, were found exclusively in black individuals. A th ird 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 Jeffer son County, Alabama. In addition, three previously undescribed point mutati ons, two of which result in amino acid substitutions, were identified withi n 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, compare d with two cases in the white population (n = 422 604) (P = 0.002). We conc lude that C6 deficiency is more common among blacks than whites in the sout h-eastern United States, with a frequency approaching 1 in 1600 black indiv iduals.