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

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Complement component C6 (C6) is crucial for forming the membrane attack complex, essential for cell defense.
• Deficiency in terminal complement components, including C6, elevates susceptibility to Neisseria infections.
• Understanding the genetic basis and prevalence of C6 deficiency is vital for public health, particularly in at-risk populations.

Purpose of the Study:

• To investigate the frequency of specific C6 loss-of-function mutations in Black and White populations.
• To identify novel C6 mutations and assess their potential impact on complement function.
• To correlate the prevalence of C6 deficiency with the incidence of meningococcal meningitis in a specific geographic area.

Main Methods:

• Genomic DNA screening using polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) analysis and DNA sequencing.
• Analysis of three known loss-of-function C6 mutations in 200 Black and 200 White individuals.
• Review of county health department records to assess meningococcal meningitis incidence by race.

Main Results:

• Two C6 mutations (1195delC and 1936delG) were exclusively found in Black individuals, while a third (878delA) occurred equally in both groups.
• C6 deficiency was significantly more common in Black individuals (P = 0.027) than White individuals in the studied population.
• A higher incidence of meningococcal meningitis (serogroups Y and W-135) was observed in Black residents, correlating with estimated C6 deficiency prevalence (P = 0.002).

Conclusions:

• C6 deficiency is more prevalent among Black individuals in the southeastern United States, with an estimated frequency of 1 in 1600.
• Genetic variations in C6 contribute to differential susceptibility to Neisseria infections between racial groups.
• The findings underscore the importance of considering genetic factors in understanding infectious disease epidemiology and disparities.