Plastic and Reconstructive Surgery Research, Epithelial Sciences, School of Translational Medicine, The Manchester Interdisciplinary Biocentre (MIB), University of Manchester, 131 Princess Street, Manchester M17ND, UK.
Arch Dermatol Res. 2010 Jul;302(5):319-39. doi: 10.1007/s00403-009-1014-y. Epub 2010 Feb 4.
Keloid scarring, also known as keloid disease (KD), is a common, abnormally raised fibroproliferative cutaneous lesion that can occur following even minor skin trauma. The aetiopathogenesis of KD has remained an enigma todate compounded by an ill-defined clinical management. There is strong evidence suggesting a genetic susceptibility in individuals affected by KD, including familial heritability, common occurrence in twins and high prevalence in certain ethnic populations. This review aims to address the genetic aspects of KD that have been described in present literature that include inheritance patterns, linkage studies, case-control association studies, whole genome gene expression microarray studies and gene pathways that were significant in KD. In addition to our clinical and scientific background in KD, we used search engines, Scopus, Scirus and PubMed, which searched for key terms covering various genetic aspects of KD. Additionally, genes reported in seven whole genome gene expression microarray studies were separately compared in detail. Our findings indicate a varied inheritance pattern in KD (predominantly autosomal dominant), linkage loci (chromosomes 2q23 and 7p11), several human leukocyte antigen (HLA) alleles (HLA-DRB115, HLA-DQA10104, DQ-B10501 and DQB10503), negative candidate gene case-control association studies and at least 25 dysregulated genes reported in multiple microarray studies. The major pathways reportedly proposed to be involved in KD include apoptosis, mitogen-activated protein kinase, transforming growth factor-beta, interleukin-6 and plasminogen activator inhibitor-1. In summary, involvement of more than one gene is likely to be responsible for susceptibility to KD. A better understanding of the genes involved in KD may potentially lead to the development of more effective diagnostic, therapeutic and prognostic measures.
瘢痕疙瘩，又称瘢痕瘤病（KD），是一种常见的异常隆起的纤维增生性皮肤病变，即使在轻微皮肤创伤后也可能发生。KD 的发病机制至今仍是一个谜，临床管理也不明确。有强有力的证据表明，KD 患者存在遗传易感性，包括家族遗传性、双胞胎中常见和某些种族人群中高发。本综述旨在探讨 KD 的遗传方面，包括遗传模式、连锁研究、病例对照关联研究、全基因组基因表达微阵列研究和 KD 中重要的基因途径。除了我们在 KD 方面的临床和科学背景外，我们还使用了搜索引擎、Scopus、Scirus 和 PubMed，这些搜索引擎搜索了涵盖 KD 各种遗传方面的关键词。此外，还详细比较了 7 项全基因组基因表达微阵列研究中报道的基因。我们的研究结果表明，KD 的遗传模式多样（主要为常染色体显性遗传）、连锁位点（染色体 2q23 和 7p11）、几个人类白细胞抗原（HLA）等位基因（HLA-DRB115、HLA-DQA10104、DQ-B10501 和 DQB10503）、阴性候选基因病例对照关联研究，以及至少 25 个在多个微阵列研究中报道的失调基因。据报道，与 KD 相关的主要途径包括细胞凋亡、丝裂原激活蛋白激酶、转化生长因子-β、白细胞介素-6 和纤溶酶原激活物抑制剂-1。综上所述，KD 的易感性可能与不止一个基因有关。对 KD 相关基因的深入了解可能有助于开发更有效的诊断、治疗和预后措施。
