Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia; School of Medicine, The University of Notre Dame Australia, Fremantle, Australia.
Centre for Genetic Origins of Health and Disease, Faculty of Health and Medical Sciences, The University of Western Australia and Faculty of Health Science, Curtin University, Perth, Australia.
Burns. 2019 May;45(3):567-578. doi: 10.1016/j.burns.2018.10.027. Epub 2018 Dec 27.
After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings.
在相似程度的损伤后，个体之间的瘢痕形成存在相当大的可变性，部分原因是遗传因素。本研究旨在确定与烧伤后瘢痕高度和柔韧性相关的遗传变异。对 665 名接受烧伤治疗的前瞻性队列进行了外显子组全基因组关联研究和基因途径分析。结局指标为改良温哥华瘢痕量表（mVSS）的瘢痕高度（SH）和瘢痕柔韧性（SP）子评分。使用 Infinium HumanCoreExome-24 BeadChip 对 DNA 进行基因分型。使用加性遗传模型，根据年龄、性别、手术次数和烧伤总面积百分比，调整欧洲血统受试者的遗传变异（单核苷酸多态性）与 SH 和 SP 的关联。没有个体遗传变异达到显著水平的截止阈值。对基因区域进行空间相关单核苷酸多态性分析，并使用 comb-p 软件识别显著区域。该基因列表进行基因途径分析，以确定哪些生物学过程术语过度表达。通过这种方法，与神经系统和细胞黏附相关的生物学过程是与 SH 和 SP 都相关的主要基因途径。本研究表明，与神经支配相关的基因可能在瘢痕纤维化中很重要。使用类似和更大的数据集进行进一步研究对于验证这些发现至关重要。
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