• Ravi F Sood, Anne M Hocking, Lara A Muffley, Maricar Ga, Shari Honari, Alexander P Reiner, and Nicole S Gibran.
• *Department of Surgery, UW Medicine Regional Burn Center, Harborview Medical Center, Seattle, WA †Department of Epidemiology, University of Washington, Seattle, WA.
• Ann. Surg. 2015 Oct 1; 262 (4): 563-9.

ObjectiveTo identify genetic variants associated with the severity of postburn hypertrophic scarring (HTS) using a genome-wide approach.BackgroundRisk of severe postburn HTS is known to depend on race, but the genetic determinants of HTS are unknown.MethodsWe conducted a genome-wide association study (GWAS) in a prospective cohort of adults admitted with deep-partial-thickness burns from 2007 through 2014. Scar severity was assessed over time using the Vancouver Scar Scale (VSS), and DNA was genotyped with a >500,000-marker array. We performed association testing of single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) >0.01 using linear regression of VSS height score on genotype adjusted for patient and injury characteristics as well as population genetic structure. Array-wide significance was based on Bonferroni correction for multiple testing.ResultsOf 538 patients (median age 40 years, median burn size 6.0% of body surface area), 71% were men and 76% were White. The mean VSS height score was 1.2 (range: 0-3). Of 289,639 SNPs tested, a variant in the CUB and Sushi multiple domains 1 (CSMD1) gene (rs11136645; MAF = 0.49), was significantly associated with decreased scar height (regression coefficient = -0.23, P = 7.9 × 10).ConclusionsIn the first published GWAS of HTS, we report that a common intronic variant in the CSMD1 gene is associated with reduced severity of postburn HTS. If this association is confirmed in an independent cohort, investigating the potential role of CSMD1 in wound healing may elucidate HTS pathophysiology.

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