期刊
ANNALS OF HUMAN GENETICS
卷 73, 期 -, 页码 171-175出版社
WILEY
DOI: 10.1111/j.1469-1809.2009.00505.x
关键词
TGFB1; Otosclerosis; rare variants
资金
- European Commission [LSHG-CT-20054-512063]
- University of Antwerp [TOP-GOA-2006]
- Flemish Fund for Scientific Research [G.0138.07]
- Institute for the Promotion of Innovation through Science and Technology in Flanders
- FWO
Otosclerosis is one of the most common forms of hearing loss in the European population. We have identified a SNP in the TGFB1 (transforming growth factor beta 1) gene that is associated with susceptibility to otosclerosis. The protective allele of this variant, with isoleucine at position 263 of the protein, is more biologically active than the risk allele, which has a threonine in this position. Because recent studies have shown that not only common, but also rare variants can be involved in complex diseases, we performed DNA sequence analysis of the exons and intron-exon boundaries of TGFB1 in 755 otosclerosis patients and 877 control samples. We found 3 different nonsynonymous variants (E29, A29 and I241) in four otosclerosis patients, but no such changes were found in controls. In silico analysis shows that these variations could influence TGF-beta 1 function and activity. Taking into account that most rare missense alleles are thought to have a biological effect, the data suggest that multiple rare amino acid changing variants in TGF-beta 1 may contribute to susceptibility to otosclerosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据