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

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2015 Jun 2

PMID 26030184

Citations 21

Authors

Ravi F Sood

Anne M Hocking

Lara A Muffley

Maricar Ga

Shari Honari

Alexander P Reiner

Ali Rowhani-Rahbar

Nicole S Gibran

Affiliations

Soon will be listed here.

Abstract

The genetic determinants of post-burn hypertrophic scarring (HTS) are unknown, and melanocortin 1 receptor (MC1R) loss-of-function leads to fibrogenesis in experimental models. To examine the associations between self-identified race and MC1R single-nucleotide polymorphisms (SNPs) with severity of post-burn HTS, we conducted a prospective cohort study of burned adults admitted to our institution over 7 years. Subjects were evaluated using the Vancouver Scar Scale (VSS), asked to rate their itching, and genotyped 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 risk factors. Of 425 subjects analyzed, 77% identified as White. The prevalence of severe HTS (VSS>7) was 49%, and the mean itch score was 3.9. In multivariate analysis, Asian (prevalence ratio (PR) 1.54; 95% CI: 1.13-2.10), Black/African American (PR 1.86; 95% CI: 1.42-2.45), and Native American (PR 1.87; 95% CI: 1.48-2.35) race were independently associated with severe HTS. MC1R SNP R163Q was also significantly (P<0.001) associated with severe HTS. Asian race (linear regression coefficient 1.32; 95% CI: 0.23-2.40) but not MC1R SNP genotype was associated with increased itch score. We conclude that MC1R genotype may influence post-burn scarring.

Citing Articles

Establishing a Collaborative Genomic Repository for Adult Burn Survivors: A Burn Model System Feasibility Study.

Sibbett S, Oh J, Carrougher G, Muffley L, Ashford N, Pacleb M Eur Burn J. 2024; 5(4):389-398.

PMID: 39727910 PMC: 11586972. DOI: 10.3390/ebj5040034.

Minority pediatric burn survivors undergo more burn operations: A single center's five-year experience.

Won P, Choe D, Gomez L, Gillenwater T, Yenikomshian H Burns. 2023; 50(3):760-766.

PMID: 37981485 PMC: 10999333. DOI: 10.1016/j.burns.2023.10.005.

Relevance and consequence of chronic inflammation for obesity development.

Ruck L, Wiegand S, Kuhnen P Mol Cell Pediatr. 2023; 10(1):16.

PMID: 37957462 PMC: 10643747. DOI: 10.1186/s40348-023-00170-6.

The Short- and Long-Term Outcome Priorities of a Western Australian Adult Burn Population.

Spronk I, Wood F, Fear M, Lansdorp C, Edgar D J Burn Care Res. 2023; 45(2):451-458.

PMID: 37936534 PMC: 10911694. DOI: 10.1093/jbcr/irad175.

[Strengthening the development and application of precision burn medicine].

Luo G, Sun X, Wu J Zhonghua Shao Shang Yu Chuang Mian Xiu Fu Za Zhi. 2023; 39(7):612-617.

PMID: 37805689 PMC: 11630206. DOI: 10.3760/cma.j.cn501225-20230407-00116.

References

Bohm M, Raghunath M, Sunderkotter C, Schiller M, Stander S, Brzoska T . Collagen metabolism is a novel target of the neuropeptide alpha-melanocyte-stimulating hormone. J Biol Chem. 2003; 279(8):6959-66. DOI: 10.1074/jbc.M312549200. View

Tomasek J, Gabbiani G, Hinz B, Chaponnier C, Brown R . Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol. 2002; 3(5):349-63. DOI: 10.1038/nrm809. View

Carrougher G, Martinez E, McMullen K, Fauerbach J, Holavanahalli R, Herndon D . Pruritus in adult burn survivors: postburn prevalence and risk factors associated with increased intensity. J Burn Care Res. 2012; 34(1):94-101. DOI: 10.1097/BCR.0b013e3182644c25. View

Lin J, Fisher D . Melanocyte biology and skin pigmentation. Nature. 2007; 445(7130):843-50. DOI: 10.1038/nature05660. View

Tredget E, Levi B, Donelan M . Biology and principles of scar management and burn reconstruction. Surg Clin North Am. 2014; 94(4):793-815. PMC: 4286257. DOI: 10.1016/j.suc.2014.05.005. View

Bohm M, Stegemann A . Bleomycin-induced fibrosis in MC1 signalling-deficient C57BL/6J-Mc1r(e/e) mice further supports a modulating role for melanocortins in collagen synthesis of the skin. Exp Dermatol. 2014; 23(6):431-3. DOI: 10.1111/exd.12409. View

Stephens J, Schneider J, Tanguay D, Choi J, Acharya T, Stanley S . Haplotype variation and linkage disequilibrium in 313 human genes. Science. 2001; 293(5529):489-93. DOI: 10.1126/science.1059431. View

Goutos I, Dziewulski P, Richardson P . Pruritus in burns: review article. J Burn Care Res. 2009; 30(2):221-8. DOI: 10.1097/BCR.0b013e318198a2fa. View

Kokot A, Sindrilaru A, Schiller M, Sunderkotter C, Kerkhoff C, Eckes B . alpha-melanocyte-stimulating hormone suppresses bleomycin-induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: melanocortin peptides as a novel treatment strategy for scleroderma?. Arthritis Rheum. 2009; 60(2):592-603. DOI: 10.1002/art.24228. View

10.

Rodriguez C, Setaluri V . Cyclic AMP (cAMP) signaling in melanocytes and melanoma. Arch Biochem Biophys. 2014; 563:22-7. DOI: 10.1016/j.abb.2014.07.003. View

11.

Purcell S, Cherny S, Sham P . Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics. 2002; 19(1):149-50. DOI: 10.1093/bioinformatics/19.1.149. View

12.

Caruso V, Lagerstrom M, Olszewski P, Fredriksson R, Schioth H . Synaptic changes induced by melanocortin signalling. Nat Rev Neurosci. 2014; 15(2):98-110. DOI: 10.1038/nrn3657. View

13.

Flanagan N, Healy E, Ray A, Philips S, Todd C, JACKSON I . Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation. Hum Mol Genet. 2000; 9(17):2531-7. DOI: 10.1093/hmg/9.17.2531. View

14.

Bell P, Gabriel V . Evidence based review for the treatment of post-burn pruritus. J Burn Care Res. 2008; 30(1):55-61. DOI: 10.1097/BCR.0b013e318191fd95. View

15.

Beaumont K, Newton R, Smit D, Leonard J, Stow J, Sturm R . Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. Hum Mol Genet. 2005; 14(15):2145-54. DOI: 10.1093/hmg/ddi219. View

16.

Tang H, Quertermous T, Rodriguez B, Kardia S, Zhu X, Brown A . Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies. Am J Hum Genet. 2004; 76(2):268-75. PMC: 1196372. DOI: 10.1086/427888. View

17.

Collins F, Varmus H . A new initiative on precision medicine. N Engl J Med. 2015; 372(9):793-5. PMC: 5101938. DOI: 10.1056/NEJMp1500523. View

18.

Brzoska T, Luger T, Maaser C, Abels C, Bohm M . Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr Rev. 2008; 29(5):581-602. DOI: 10.1210/er.2007-0027. View

19.

Gerstenblith M, Goldstein A, Fargnoli M, Peris K, Landi M . Comprehensive evaluation of allele frequency differences of MC1R variants across populations. Hum Mutat. 2007; 28(5):495-505. DOI: 10.1002/humu.20476. View

20.

Gauglitz G, Korting H, Pavicic T, Ruzicka T, Jeschke M . Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2010; 17(1-2):113-25. PMC: 3022978. DOI: 10.2119/molmed.2009.00153. View