MC1R gene polymorphisms are associated with dysfunctional immune responses and wound infection after burn injury

Abstract

Background: Systemic inflammatory response syndrome (SIRS) is associated with organ failure and infectious complications after major burn injury. Recent evidence has linked melanocortin signaling to anti-inflammatory and wound-repair functions, with mutations in the melanocortin 1 receptor (MC1R) gene leading to increased inflammatory responses. Our group has previously demonstrated that MC1R gene polymorphisms are associated with postburn hypertrophic scarring. Thus, we hypothesized that MC1R single nucleotide polymorphisms (SNPs) would be associated with increased burn-induced SIRS and increased infectious complications. Methods: We performed a retrospective cohort study of adults (>18 y of age) admitted to our burn center with >20% total body surface area (TBSA) partial/full thickness burns between 2006 and 2013. We screened for five MC1R SNPs (V60L, V92M, R151C, R163Q, T314T) by polymerase chain reaction from genomic DNA isolated from blood samples. We performed a detailed review of each patient chart to identify age, sex, race, ethnicity, %TBSA burned, burn wound infections (BWIs), and 72-hr intravenous fluid volume, the latter a surrogate for a dysfunctional inflammatory response to injury. Association testing was based on multivariable regression. Results: Of 106 subjects enrolled, 82 had complete data for analysis. Of these, 64 (78%) were male, with a median age of 39 and median burn size of 30% TBSA. A total of 36 (44%) subjects developed BWIs. The median total administered IV crystalloid in first 72h was 24.6 L. In multivariate analysis, the R151C variant allele was a significant independent risk factor for BWI (adjusted prevalence ratio 2.03; 95% CI: 1.21–3.39; P = 0.007), and the V60L variant allele was independently associated with increased resuscitation fluid volume (P = 0.021). Conclusions: This is the first study to demonstrate a significant association between genetic polymorphisms and a nonfatal burn-induced SIRS complication. Our findings suggest that MC1R polymorphisms contribute to dysfunctional responses to burn injury that may predict infectious and inflammatory complications.

Effect of whole course seamless nursing mode on patients with chronic infectious wounds

“…Chronic infectious wounds refer to wounds (due to various factors) infected with microorganisms during the healing stage, which are common in surgery 5 - 7 . The recovery of chronic infectious wounds is intractable, which is prone to delayed wound healing or even unhealed wounds, seriously affecting the daily life of patients 8 - 10 . In addition, long-term unhealed wounds will cause severe pain, affecting the psychological state and sleep status of patients 11 , 12 .…”

Melanocortin‐1 receptor influence in equine opioid sensitivity

“…In addition to its widely accepted roles in pigmentation, the MC1R gene has also been correlated with anxiety, being seen as a significant predictor of dental care-related anxiety in humans (Binkley et al, 2009). The MC1R gene has also been implicated in burn injury complications, with human studies showing MC1R polymorphisms may contribute to systemic infectious response syndrome associated with infectious complications and organ failure following major burn injury (Carter et al, 2018). Pheomelanin pigment pathways resultant from MC1R polymorphisms have also been attributed to ultraviolet-radiation independent melanoma carcinogenesis via a mechanism of oxidative damage, with variants presenting the highest melanoma risk (Chen et al, 2017a(Chen et al, , 2017bMitra et al, 2012;Tell-Marti et al, 2020).…”

<p>Identification of Key Genes Associated with Changes in the Host Response to Severe Burn Shock: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database</p>

“… 11 Carter found that the melanocortin 1 receptor ( MC1R ) gene polymorphism was associated with wound infection after burn injury. 12 In the repair stage after burn injury, nucleotide-binding domain leucine-rich repeat ( NLR ) and pyrin domain containing receptor 3 ( NLRP3 ) promote wound healing through regulation of macrophage polarization and inflammation. 13 However, there has been little information regarding the important genes expressed during burn shock.…”