Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Am J Med Genet A. 2012 May;158A(5):1066-70. doi: 10.1002/ajmg.a.35276. Epub 2012 Apr 9.
Otosclerosis is a disease of abnormal bone remodeling in the human otic capsule that can lead to progressive hearing loss. Little of the underlying disease etiology has been elucidated thus far, although several studies have suggested that COL1A1 may play a role based on its importance in bone metabolism and other diseases like osteoporosis and osteogenesis imperfecta. Genetic association studies between COL1A1 and otosclerosis, however, have been contradictory. To resolve this issue, we studied a large Belgian-Dutch and a Swiss population for a genetic association between COL1A1 and otosclerosis and additionally performed a meta-analysis to investigate the overall genetic effect of COL1A1 on all otosclerosis populations studied to date. We found a significant association both in the Belgian-Dutch population and in the meta-analysis. In aggregate, our analysis supports evidence for an association between COL1A1 and otosclerosis although effect sizes of the variants reported in the initial studies are likely to be an overestimate of true effect sizes.
耳硬化症是一种人类耳壳骨重塑异常的疾病，可导致进行性听力损失。迄今为止，尽管有几项研究表明，COL1A1 在骨代谢和骨质疏松症、成骨不全症等其他疾病中具有重要作用，但其潜在的疾病病因仍未得到充分阐明。然而，COL1A1 与耳硬化症之间的遗传关联研究存在矛盾。为了解决这个问题，我们对一个大型的比利时-荷兰和瑞士人群进行了研究，以确定 COL1A1 与耳硬化症之间是否存在遗传关联，此外还进行了荟萃分析，以调查 COL1A1 对迄今为止所有研究的耳硬化症人群的总体遗传效应。我们发现无论是在比利时-荷兰人群还是在荟萃分析中，都存在显著的关联。总的来说，我们的分析支持 COL1A1 与耳硬化症之间存在关联的证据，尽管最初研究中报告的变异体的效应大小可能高估了真实的效应大小。
