The purpose of this study is to identify the gene or genes responsible for keloid formation.
Keloids are raised scars on the skin that form after a minor injury. A tendency to develop
keloids often runs in families, suggesting a possible genetic basis.
People who have had a classic (butterfly-shaped or wound-overflowing) keloid for at least
one year may be eligible for this study. In addition to these probands (original
participants), family members over 12 years of age who have either classic or non-classic
keloids and those 18 years of age or older without keloids may participate.
Probands and family members with keloids will have a medical history focusing on skin
problems particularly keloids and a skin examination. In some cases, with the subject s
permission, photos of the keloids will be taken. All participants will have 35 milliliters
(about 2 tablespoons) of blood drawn for DNA (genetic) testing and for measurement of blood
proteins, including cytokines, which can affect other tissues and cause scarring. Part of
the blood sample will be used for additional genetic studies unrelated to keloids. The
samples will be coded for confidentiality.
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:
1. Proband: must have a butterfly-shaped or wound-overflowing keloid, present for
at least one year (this description represents classic keloid, and avoids
2. 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.
3. Unaffected family members: all family members who lack keloids.
4. Impaired subjects for whom a legal guardian provides consent.
5. Pregnant women.
1. Subjects who are unwilling or unable to give informed consent or assent.
2. Impaired individuals from whom it not possible to obtained parental consent (minors)
or guardian consent (adults).
3. Keloid patients who have <3 relatives with keoids.