背景:尽管亨廷顿病(HD)在韩国的流行病学与西方国家有明显的不同,这些区域之间的遗传差异仍不清楚.
目的:探讨韩国人群中与HD相关的胞嘧啶-腺嘌呤-鸟嘌呤(CAG)重复序列大小的特点及临床意义。
方法:我们分析了韩国两家转诊医院的941名健康个体(1,882个等位基因)和954名舞蹈病患者(1,908个等位基因)的HTT基因的CAG重复长度。我们提供了韩国人群的标准CAG重复长度数据,并计算了两组中降低的外显率(36-39CAG)和中间等位基因(27-35CAG)频率。此外,我们使用logistic回归模型在≥55岁的个体中调查了中间等位基因与舞蹈病发展之间的关系。
结果:健康个体的平均(±标准差)CAG重复长度为17.5±2.0,降低的外显等位基因频率为0.05%(1/1882),中间等位基因频率为0.69%(13/1882)。我们确定了213例遗传证实的HD患者,其CAG重复长度范围为39至140,较长等位基因的平均值为45.2±7.9。与正常CAG重复等位基因相比,中间CAG重复等位基因与发生舞蹈病的高风险显著相关(发病年龄范围,63-84岁)年龄≥55岁的个体。
结论:这项研究提供了对韩国人群HTT基因中CAG重复长度的具体特征的见解。韩国普通人群的外显率和中间等位基因频率降低似乎低于西方人群的报道。中间等位基因的存在可能会增加韩国老年人患舞蹈病的风险,这需要进一步的大规模调查。
BACKGROUND: Although the epidemiology of Huntington\'s disease (HD) in Korea differs notably from that in Western countries, the genetic disparities between these regions remain unclear.
OBJECTIVE: To investigate the characteristics and clinical significance of cytosine-adenine-guanine (CAG) repeat size associated with HD in the Korean population.
METHODS: We analyzed the CAG repeat lengths of the HTT gene in 941 healthy individuals (1,882 alleles) and 954 patients with chorea (1,908 alleles) from two referral hospitals in Korea. We presented normative CAG repeat length data for the Korean population and computed the reduced penetrance (36-39 CAG) and intermediate allele (27-35 CAG) frequencies in the two groups. Furthermore, we investigated the relationship between intermediate alleles and chorea development using logistic regression models in individuals aged ≥55 years.
RESULTS: The mean (±standard deviation) CAG repeat length in healthy individuals was 17.5 ± 2.0, with a reduced penetrance allele frequency of 0.05 % (1/1882) and intermediate allele frequency of 0.69 % (13/1882). We identified 213 patients with genetically confirmed HD whose CAG repeat length ranged from 39 to 140, with a mean of 45.2 ± 7.9 in the longer allele. Compared with normal CAG repeat alleles, intermediate CAG repeat alleles were significantly related to a higher risk of developing chorea (age of onset range, 63-84 years) in individuals aged ≥55 years.
CONCLUSIONS: This study provides insights into the specific characteristics of CAG repeat lengths in the HTT gene in the Korean population. The reduced penetrance and intermediate allele frequencies in the Korean general population seem to be lower than those reported in Western populations. The presence of intermediate alleles may increase the risk of chorea in the Korean elderly population, which requires further large-scale investigations.