Arning Larissa, Jagiello Peter, Wieczorek Stefan, Saft Carsten, Andrich Jürgen, Epplen Jörg T
Department of Human Genetics, Ruhr-University, 44780 Bochum, Germany.
BMC Med Genet. 2004 Mar 24;5:7. doi: 10.1186/1471-2350-5-7.
Huntington's disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Circumstantial evidence suggests that additional features of the HD course are based on genetic traits. Therefore, it may be possible to investigate the genetic background of HD, i.e. to map the loci underlying the development and progression of the disease. Recently an association of Glutathione S-Transferase Omega 1 (GSTO1) and possibly of GSTO2 with AO was demonstrated for, both, Alzheimer's (AD) and Parkinson's disease (PD).
We have genotyped the polymorphisms rs4925 GSTO1 and rs2297235 GSTO2 in 232 patients with HD and 228 controls.
After genotyping GSTO1 and GSTO2 polymorphisms, firstly there was no statistically significant difference in AO for HD patients, as well as secondly for HD patients vs. controls concerning, both, genotype and allele frequencies, respectively.
The GSTO1 and GSTO2 genes flanked by the investigated polymorphisms are not comprised in a primary candidate region influencing AO in HD.
亨廷顿舞蹈症(HD)是一种完全显性的常染色体显性遗传疾病,与IT15基因5'端一段完美的CAG重复序列异常扩增有关。重复单元的数量对该疾病的发病年龄(AO)具有高度预测性。但在考虑中等程度的HD扩增时,AO与重复长度仅呈适度相关。间接证据表明,HD病程的其他特征基于遗传特性。因此,有可能研究HD的遗传背景,即绘制该疾病发生和发展的潜在基因座。最近,已证明谷胱甘肽S-转移酶ω1(GSTO1)以及可能的GSTO2与阿尔茨海默病(AD)和帕金森病(PD)的发病年龄均存在关联。
我们对232例HD患者和228例对照者的rs4925 GSTO1和rs2297235 GSTO2多态性进行了基因分型。
对GSTO1和GSTO2多态性进行基因分型后,首先,HD患者的发病年龄在统计学上没有显著差异,其次,HD患者与对照者在基因型和等位基因频率方面也没有显著差异。
所研究的多态性侧翼的GSTO1和GSTO2基因并不在影响HD发病年龄的主要候选区域内。