Department of Surgery, University of Washington, Seattle, Washington.
Stritch School of Medicine, Loyola University Chicago, Chicago, Illinois.
Ann Surg. 2022 May 1;275(5):1002-1005. doi: 10.1097/SLA.0000000000004235. Epub 2020 Sep 24.
Associations between genetic variation and clinical conditions suggest that single nucleotide polymorphisms (SNPs) might correlate with postburn outcomes. COMT modulates catecholamine metabolism, and polymorphisms within the rs4680 allele result in variable enzyme activity. Catechol-amines are known to modulate the inflammatory process and may affect scar formation. The aim of this study was to determine whether variants in the rs4680 SNP of the COMT gene are associated with post-burn pruritus and scarring.
Adult burn patients, admitted between 2007 and 2017, with deep partial-thickness burns or delayed healing provided blood samples for genotyp-ing and self-reported itch scores within 1 year of injury. Scarring was measured using the Vancouver Scar Scale (VSS). Itch scores ≥ 4 and VSS scores >7 were considered severe. Genomic deoxyribonucleic acid was genotyped for the rs4680 SNP using realtime polymerase chain reaction (PCR).
Median itch and VSS scores were highest for GG homozygotes and lowest for AA homozygotes. This difference was statistically significant for VSS score (P < 0.0001) and approached significance for itch (P = 0.052). After accounting for confounding variables, including race/ethnicity, age, sex, and burn size, the GG homozygotes demonstrated worse scarring (odds ratio 1.88, P = 0.005) compared to AG heterozygotes whereas the AA homozygotes trended towards a protective effect against scarring (odds ratio 0.71, P = 0.10). itch did not demonstrate a statistically significant difference between rs4680 genotype.
Our analysis identifies a trend between COMT genotype with scarring, with rs4680 genetic variation constituting an independent risk factor for VSS score.
遗传变异与临床状况之间的关联表明,单核苷酸多态性(SNP)可能与烧伤后结果相关。COMT 调节儿茶酚胺代谢,rs4680 等位基因内的多态性导致酶活性的可变性。儿茶酚胺已知可调节炎症过程,并可能影响瘢痕形成。本研究旨在确定 COMT 基因 rs4680 单核苷酸多态性与烧伤后瘙痒和瘢痕形成是否相关。
2007 年至 2017 年间,成年烧伤患者因深度部分厚度烧伤或延迟愈合而入院,在受伤后 1 年内提供血液样本进行基因分型和自我报告瘙痒评分。使用温哥华瘢痕量表(VSS)测量瘢痕形成。瘙痒评分≥4 分和 VSS 评分>7 分被认为是严重的。使用实时聚合酶链反应(PCR)对 rs4680 SNP 进行基因组脱氧核糖核酸基因分型。
GG 纯合子的瘙痒和 VSS 评分中位数最高,AA 纯合子最低。VSS 评分(P < 0.0001)差异具有统计学意义,瘙痒评分接近统计学意义(P = 0.052)。在考虑混杂变量,包括种族/民族、年龄、性别和烧伤面积后,GG 纯合子与 AG 杂合子相比,瘢痕形成更差(比值比 1.88,P = 0.005),而 AA 纯合子显示出对瘢痕形成的保护作用(比值比 0.71,P = 0.10)。瘙痒在 rs4680 基因型之间没有显示出统计学上的显著差异。
我们的分析确定了 COMT 基因型与瘢痕形成之间的趋势,rs4680 遗传变异是 VSS 评分的独立危险因素。