Keloids are benign fibrotic dermal tumors that form during prolonged wound healing. Keloids are characterized by an exaggerated response to injury and a prevalence disparity between African and non-African populations. Keloids occur in ~1/30 African Americans (AAs) with a 20-fold higher risk in AAs than in European Americans (EAs). Due to the high prevalence of keloids among AA and evidence that keloids are heritable, we conducted admixture mapping to determine if local ancestry associated with keloid risk. We observed strong evidence of ancestry associating with keloid risk at chr15q21.2-22.3 that included NEDD4, a gene previously implicated with keloids. However, the strongest associations were in a nearby gene, MYO1E. Evaluation of MYO1E expression showed increased expression in fibroblasts from keloid relative to normal scar tissue. We are currently identifying novel variants associated with keloids by resequencing genes in chr15q21.2-22.3 and validating in an independent cohort. We are also evaluating the biological relevance of candidate keloid loci or genes associated with keloid formation by using a well-characterized fibroblast strains from keloids and normal scars on up to ten genes to see what effects manipulation of their expression has on keloid and normal phenotypes in culture.
Hellwege JN, Russell SB, Williams SM, Edwards TL, Velez Edwards DR. Gene-based evaluation of low-frequency variation and genetically-predicted gene expression impacting risk of keloid formation. Ann. Hum. Genet [print-electronic]. 2018 Feb 2/27/2018; PMID: 29484647, DOI: 10.1111/ahg.12245, ISSN: 1469-1809.
Velez Edwards DR, Tsosie KS, Williams SM, Edwards TL, Russell SB. Admixture mapping identifies a locus at 15q21.2-22.3 associated with keloid formation in African Americans. Hum. Genet [print-electronic]. 2014 Dec; 133(12): 1513-23. PMID: 25280642, PMCID: PMC4334317, DOI: 10.1007/s00439-014-1490-9, ISSN: 1432-1203.