McCarty Sara, Syed Farhatullah, Bayat Ardeshir
University of Manchester, Manchester, UK.
Hand (N Y). 2010 Sep;5(3):241-50. doi: 10.1007/s11552-009-9255-y. Epub 2010 Feb 9.
Dupuytren's disease (DD) is a familial, fibroproliferative, irreversible, and progressive disease of the palmar fascia, yet with unknown etiology. However, there is compelling evidence which has consistently suggested a genetic ethiopathogenesis given the high occurrence among the Northern European extraction, familial nature, and demonstration of concordance in twins. DD is an incurable, recurrent, and potentially debilitating disease with limited and ineffective treatments. Although a number of possible candidate genes have been investigated including matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-β) genes, as yet, no consistent genetic biomarker has been identified for DD. The highly polymorphic human leukocyte antigen (HLA) region is an ideal biomarker target. There have been some coherent data within the literature to suggest a genotype to phenotype association between certain HLA loci and a number of fibrotic disorders such as keloid and scleroderma, markedly with class II molecules and disease pervasiveness and clinical progression. The aim of this review, therefore, was to investigate the evidence indicative of both positive and negative associations between particular HLA alleles and DD. There is a clear association with specific HLA alleles and predilection or protection to DD, though there is a pressing need for further supportive data. The most promising of links to the HLA region in terms of a definitive genetic biomarker is with the class II HLA-DR loci. This paper presents a detailed account of the immunogenetic component of DD and explores the possible mechanisms of association between specific HLA molecules and susceptibility to DD.
杜普伊特伦挛缩症（DD）是一种家族性、纤维增生性、不可逆且进行性发展的掌腱膜疾病，但其病因尚不清楚。然而，鉴于北欧血统人群中该病的高发病率、家族性特征以及双胞胎的一致性表现，有令人信服的证据一直表明其存在遗传病因发病机制。DD是一种无法治愈、易复发且可能导致功能障碍的疾病，治疗方法有限且效果不佳。尽管已经对包括基质金属蛋白酶（MMPs）和转化生长因子-β（TGF-β）基因在内的一些可能的候选基因进行了研究，但迄今为止，尚未确定DD的一致遗传生物标志物。高度多态的人类白细胞抗原（HLA）区域是理想的生物标志物靶点。文献中有一些连贯的数据表明，某些HLA基因座与瘢痕疙瘩和硬皮病等多种纤维化疾病之间存在基因型与表型的关联，特别是与II类分子以及疾病的普遍性和临床进展有关。因此，本综述的目的是研究特定HLA等位基因与DD之间正相关和负相关的证据。特定HLA等位基因与DD的易感性或保护性之间存在明确关联，不过迫切需要更多支持性数据。就确定的遗传生物标志物而言，与HLA区域最有希望的联系是与II类HLA-DR基因座。本文详细阐述了DD的免疫遗传成分，并探讨了特定HLA分子与DD易感性之间可能的关联机制。
