Gene-based evaluation of low-frequency variation and genetically-predicted gene expression impacting risk of keloid formation.

Keloids are benign dermal tumors occurring approximately 20 times more often in individuals of African descent as compared to individuals of European descent. While most keloids occur sporadically, a genetic predisposition is supported by both familial aggregation of some keloids and large differences in risk among populations. Despite Africans and African Americans being at increased risk over lighter-skinned individuals, little genetic research exists into this phenotype.

Evidence of selection as a cause for racial disparities in fibroproliferative disease.

Fibroproliferative diseases are common complex traits featuring scarring and overgrowth of connective tissue which vary widely in presentation because they affect many organ systems. Most fibroproliferative diseases are more prevalent in African-derived populations than in European populations, leading to pronounced health disparities. It is hypothesized that the increased prevalence of these diseases in African-derived populations is due to selection for pro-fibrotic alleles that are protective against helminth infections.

Pleiotropic Effects of Immune Responses Explain Variation in the Prevalence of Fibroproliferative Diseases.

Many diseases are differentially distributed among human populations. Differential selection on genetic variants in ancestral environments that coincidentally predispose to disease can be an underlying cause of these unequal prevalence patterns. Selected genes may be pleiotropic, affecting multiple phenotypes and resulting in more than one disease or trait.

Admixture mapping identifies a locus at 15q21.2-22.3 associated with keloid formation in African Americans.

Keloids are benign dermal tumors that occur ~20 times more often in African versus Caucasian descent individuals. While most keloids occur sporadically, a genetic predisposition is supported by both familial aggregation of some keloids and the large differences in risk among populations. Yet, no well-established genetic risk factors for keloids have been identified.

Epigenetically altered wound healing in keloid fibroblasts.

Keloids are benign dermal tumors that form during wound healing in genetically susceptible individuals. The mechanism(s) of keloid formation is unknown and there is no satisfactory treatment. We have reported differences between fibroblasts cultured from normal scars and keloids that include a pattern of glucocorticoid resistance and altered regulation of genes in several signaling pathways associated with fibrosis, including Wnt and IGF/IGF-binding protein 5 (IGFBP5).

The legacy of the regional research centers for minority oral health.

The Regional Research Centers for Minority Oral Health (RRCMOH) helped to redefine the research and education missions of the participating institutions, and placed new emphasis on early diagnosis, prevention, and conservative interventions in minority-related oral diseases, with an eye toward innovative, cost-effective solutions to long-neglected and underfunded areas of dental and craniofacial research, education, and health promotion programs. This article reviews the legacy of the RRCMOH.