title: A non-conservative, coding single-nucleotide polymorphism in the N-terminal region of lactoferrin is associated with aggressive periodontitis in an African-American, but not a Caucasian population.
abstract: Lactoferrin is an antimicrobial protein which plays an important role in regulating bacteria that are associated with aggressive periodontitis. Lactoferrin kills directly (via its strongly cationic N-terminal region) and indirectly, through sequestering the iron that bacteria require for growth. As aggressive periodontitis has a strong heritable component, we hypothesized that genetic variation within the lactoferrin gene may play a role in susceptibility to this condition. We have identified and examined a novel, functional, single-point A/G nucleotide mutation causing a threonine/alanine substitution at position 11 (T11A) of the secreted lactoferrin protein. In a pilot case-controlled study of aggressive periodontitis, analysis of 46 African-American patients and 78 controls showed that patients were twice as likely to express the G nucleotide (alanine) allele over controls (60.3 vs 30.4%; P=0.0007, odds ratio=2.564, 95% CI=1.475-4.459). A Caucasian population of 77 patients and 131 controls showed no such association (P=0.5201, odds ratio=0.862, 95% CI=0.548-1.356). The data presented provide a new insight into the genetic susceptibility to aggressive periodontitis.
authors.affiliation: Department of Oral Biology, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Jordan
authors.forename: J
authors.initials: J
authors.lastname: Eskdale
authors.forename: G P
authors.initials: GP
authors.lastname: Lennon
authors.forename: R
authors.initials: R
authors.lastname: Pestoff
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: D H
authors.initials: DH
authors.lastname: Fine
authors.forename: G
authors.initials: G
authors.lastname: Gallagher
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D017124:Conserved Sequence; D005260:Female; D006801:Humans; D007781:Lactoferrin / Q000235:genetics*; D008297:Male; D010518:Periodontitis / Q000208:ethnology / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D013912:Threonine / Q000235:genetics; D044465:White People
chemical_list: D013912:Threonine; D007781:Lactoferrin; D000409:Alanine