Genetic Analysis of Familial Keloids

Keloids represent a pathologic fibrosis which occurs in the skin after trauma and which grow beyond the boundaries of injury. Keloids occur in people of all racial backgrounds; however, individuals of African descent are more susceptible to the disease. A familial disposition to keloid formation has long been recognized, but the genetic basis for this racial and familial predisposition has not been identified. We hypothesize that the increased risk is a direct result of one or more disease susceptibility genes. We will pursue two approaches, which are presented as two study modules. In module 1, we will carry out a family study. We will identify affected pedigrees, each containing at least 3 individuals with keloids. Blood will be obtained and Epstein Barr virus-transformed permanent B cell lines will be established. We anticipate taking two analytic strategies. We will use candidate gene analysis, focusing initially on the CBP and TGF1B genes and a recently identified locus on chromosome 14, and we will use genome-wide markers to identify possible disease gene loci. In module 2, we will perform a genome scan to address the hypothesis that one or more African origin genetic variants account for the excess prevalence of keloids among African Americans. We will carry out a mapping by admixture linkage disequilibrium (MALD) scan, in order to find genetic regions where differences in the distribution of particular tagging single nucleotide polymorphisms (SNPs) between keloid cases and controls indicate excess African ancestry. Further analysis of these loci will be carried out to identify the causative genetic variants.

• INCLUSION CRITERIA:

• Proband: must have a butterfly-shaped or wound-overflowing keloid, present for at least one year (this description represents classic keloid, and avoids hypertrophic scar)
• Affected family members: all family members of the proband who have either classic keloids, as described above, or non-classic keloids, such as ball shaped-keloids on the ear.
• Unaffected family members: all family members who lack keloids.
• Impaired subjects for whom a legal guardian provides consent.
• Pregnant women.

EXCLSUION CIRTERIA:

• Subjects who are unwilling or unable to give informed consent or assent.
• Impaired individuals from whom it not possible to obtained parental consent (minors) or guardian consent (adults).
• Keloid patients who have <3 relatives with keoids.