Race and Melanocortin 1 Receptor Polymorphism R163Q Are Associated with Post-Burn Hypertrophic Scarring: A Prospective Cohort Study

Sood, Ravi F.; Hocking, Anne M.; Muffley, Lara A.; Ga, Maricar; Honari, Shari; Reiner, Alexander P.; Rowhani-Rahbar, Ali; Gibran, Nicole S.

doi:10.1038/jid.2015.197

Cited by 40 publications

(47 citation statements)

References 49 publications

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“…In addition to increased risk of morbidity and mortality in the immediate post-burn period, larger burns are also associated with increased severity of hypertrophic scarring (39), a common long-term sequela of burn injury that results in stiff, raised, contracted scars associated with disfigurement, functional limitation, and decreased quality of life (40). The mechanism connecting burn size to increased scar severity is currently unknown, and a wide range of circulating immune cells and factors have been implicated in HTS formation (41).…”

Section: Discussionmentioning

confidence: 99%

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults

Sood

Gibran

Arnoldo

et al. 2016

Journal of Trauma and Acute Care Surgery

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Background In the burn-injured patient, older age, larger percent total body surface area (%TBSA) burned, and inhalation injury are established risk factors for death, which typically results from multisystem organ failure and sepsis, implicating burn-induced immune dysregulation as a contributory mechanism. We sought to identify early transcriptomic changes in circulating leukocytes underlying increased mortality associated these three risk factors. Methods We performed a retrospective analysis of the Glue Grant database. From 2003–2010, 324 adults with ≥20% TBSA burned were prospectively enrolled at five US burn centers, and 112 provided blood samples within one week post-burn. RNA was extracted from pooled leukocytes for hybridization onto Affymetrix HU133 Plus 2.0 GeneChips. A multivariate regression model was constructed to determine risk factors for mortality. Testing for differential gene association associated with age, burn size, and inhalation injury was based on linear models using a fold-change threshold of 1.5 and false-discovery rate of 0.05. Results After adjusting for potential confounders, age >60 (RR 4.53; 95% CI: 2.93–6.99), burn size >40% TBSA (RR 4.24; 95% CI: 2.61–6.91), and inhalation injury (RR 2.08; 95% CI: 1.35–3.21) were independently associated with mortality. No genes were differentially expressed in association with age >60 or inhalation injury. Fifty-one probe sets representing thirty-nine unique genes were differentially expressed in leukocytes from patients with burn size >40% TBSA; these genes were associated with platelet activation and degranulation/exocytosis, and gene-set enrichment analysis suggested increased cellular proliferation and down-regulation of pro-inflammatory cytokines. Conclusions Among adults with large burns, older age, increasing burn size, and inhalation injury have a modest effect on the leukocyte transcriptome in the context of the “genomic storm” induced by a ≥20% TBSA burn. The 39-gene signature we identified may provide novel targets for the development of therapies to reduce morbidity and mortality associated with burns >40% TBSA. Level of Evidence Epidemiologic study, level III.

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Section: Discussionmentioning

confidence: 99%

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults

Sood

Gibran

Arnoldo

et al. 2016

Journal of Trauma and Acute Care Surgery

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“…18,19 Several factors were shown to influence scar formation and scar quality. Patients with a darker skin type, 20-22 more operations, 21,23 full thickness wounds, 18,20,24 a high percentage total body surface area (%TBSA) burned, 18,20,24 and delayed wound healing 23,[25][26][27] have a higher risk of reduced scar quality. As the maturation of scars may take several years, it is also important to assess scar quality and factors associated with scar quality in the long-term.…”

Section: Posasmentioning

confidence: 99%

Patient‐reported scar quality of adults after burn injuries: A five‐year multicenter follow‐up study

Spronk

Polinder

Haagsma

et al. 2019

Wound Repair Regeneration

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Scar formation is an important adverse consequence of burns. How patients appraise their scar quality is often studied shortly after sustaining the injury, but information in the long‐term is scarce. Our aim was, therefore, to evaluate long‐term patient‐reported quality of burn scars. Adults with a burn center admission of ≥1 day between August 2011 and September 2012 were invited to complete a questionnaire on long‐term consequences of burns. We enriched this sample with patients with severe burns (>20% total body surface area [TBSA] burned or TBSA full thickness >5%) treated between January 2010 and March 2013. Self‐reported scar quality was assessed with the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS). Patients completed this scale for their—in their opinion—most severe scar ≥5 years after burns. This study included 251 patients with a mean %TBSA burned of 10%. The vast majority (91.4%) reported at least minor differences with normal skin (POSAS item score ≥2) on one or more scar characteristics and 78.9% of the patients’ overall opinion was that their scar deviated from normal skin. Patients with severe burns had higher POSAS scores, representing worse scar quality, than patients with mild/intermediate burns, except for color, which was high in both groups. A longer hospital stay predicted reduced scar quality (both mean POSAS and mean overall opinion of the scar) in multivariate analyses. In addition, female gender was also associated with a poorer overall opinion of the scar. In conclusion, this study provides new insights in long‐term scar quality. Scars differed from normal skin in a large part of the burn population more than 5 years after burns, especially in those with severe burns. Female gender is associated with a poorer patients’ overall opinion of their scar, which may be an indication of gender differences in perception of scar quality after burns.

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“…Physiologically, hypomorphic variants of MC1R lead to reduced intracellular cAMP synthesis and are associated with the red hair pale skin phenotype in humans . In the context of wound healing, it is puzzling to note a recent a prospective cohort study of burned adult Black/African American and native American race that were independently associated with severe postburn hypertrophic scarring . The MC1R single nucleotide polymorphism SNP R163Q was significantly associated with severe postburn hypertrophic scarring.…”

Section: Discussionmentioning

confidence: 99%

Are melanocortin peptides future therapeutics for cutaneous wound healing?

Böhm

Luger

2019

Experimental Dermatology

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Cutaneous wound healing is a complex process divided into different phases, that is an inflammatory, proliferative and remodelling phase. During these phases, a variety of resident skin cell types but also cells of the immune system orchestrate the healing process. In the last year, it has been shown that the majority of cutaneous cell types express the melanocortin 1 receptor (MC1R) that binds α‐melanocyte‐stimulating hormone (α‐MSH) with high affinity and elicits pleiotropic biological effects, for example modulation of inflammation and immune responses, cytoprotection, antioxidative defense and collagen turnover. Truncated α‐MSH peptides such as Lys‐Pro‐Val (KPV) as well as derivatives like Lys‐d‐Pro‐Thr (KdPT), the latter containing the amino acid sequence 193‐195 of interleukin‐1β, have been found to possess anti‐inflammatory effects but to lack the pigment‐inducing activity of α‐MSH. We propose here that such peptides are promising future candidates for the treatment of cutaneous wounds and skin ulcers. Experimental approaches in silico, in vitro, ex vivo and in animal models are outlined. This is followed by an unbiased discussion of the pro and contra arguments of such peptides as future candidates for the therapeutic management of cutaneous wounds and a review of the so‐far available data on melanocortin peptides and derivatives in wound healing.

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Race and Melanocortin 1 Receptor Polymorphism R163Q Are Associated with Post-Burn Hypertrophic Scarring: A Prospective Cohort Study

Cited by 40 publications

References 49 publications

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults

Patient‐reported scar quality of adults after burn injuries: A five‐year multicenter follow‐up study

Are melanocortin peptides future therapeutics for cutaneous wound healing?

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