Race, ethnicity, and melanocortin-1-receptor polymorphisms are associated with post-burn hypertrophic scarring: a prospective cohort study

Abstract

Objective: To assess the association between melanocortin 1 receptor (MC1R) single-nucleotide polymorphisms (SNPs) and severity of post-burn hypertrophic scarring (HTS). Background: People of color seem predisposed to HTS, but this association has not been quantified, nor have genetic factors been identified. Recent evidence indicates that melanocortin signaling has an anti-inflammatory effect, and MC1R loss-of-function is associated with fibrogenesis. Methods: Between 2007 and 2013 we prospectively enrolled adults admitted with deep burns and obtained blood for DNA isolation. Subjects were evaluated over time using the Vancouver Scar Scale (VSS) and asked to rate their itching. Genotyping was performed for 8 MC1R SNPs. Testing for association with severe HTS (VSS>7) and itch severity (0-10) was based on multivariate regression with adjustment for known HTS risk factors. Results: Of 425 subjects, (median burn size 6.8% body surface area), 77% were White and 88% were non-Hispanic. The prevalence of severe HTS (VSS>7) was 49%, and the mean itch score was 3.9. In multivariate analysis, Hispanic ethnicity (prevalence ratio [PR] 1.32) and Asian (PR 1.61), Black/African American (PR 1.95), and Native American (PR 1.84) race were independently associated with severe HTS. Two MC1R SNPs, R151C (P = 0.033) and R163Q (P = 0.005), were significantly associated with severe HTS. Hispanic ethnicity and Asian race were associated with increased pruritus, and MC1R T314T was associated with decreased pruritus. Conclusions: Race and ethnicity are significantly associated with post-burn HTS and itch severity, and MC1R R151C and R163Q are the first SNPs to be associated with post-burn HTS.