Association between the HLA-A2 allele and Alzheimer disease
Association between the HLA-A2 allele and Alzheimer disease
复制标题
DOI：
10.1089/rej.2006.9.99
复制
发表时间：
2006-03-01
影响因子：
2.6
通讯作者：
Caruso, C
中科院分区：
文献类型：
--
作者：
Listì, F;Candore, G;Caruso, C
在老年人中，痴呆症最常见的原因是阿尔茨海默病（AD），它是由疾病介导的与年龄相关的进行性神经退行性炎症状况的原因。已经看到，一些遗传和环境因素参与AD发病。流行病学数据表明，AD的一些遗传决定因素可能存在于那些调节免疫炎症反应的多态性，如主要组织相容性复合体（MHC）。因此，一些MHC多态性已成为大量AD关联研究的焦点。HLA-A2等位基因与AD易感性增加的可能关联已成为20多年来争论的主题，即使这些研究在不同人群中的结果不一致。因此，为了深入了解这一问题，作者研究了HLA-A2等位基因与意大利患者同质人群中散发性AD的可能关联。为此，我们采用PCR-SSP方法分析了散发性AD患者和对照组中HLA-A2等位基因的分布。结果表明，散发性AD患者与对照组之间HLA-A2等位基因的频率有显著差异（46%对38%）。因此，这些数据证实了HLA-A2等位基因在发展AD的风险中的积极作用。然而，一些观察到的差异可能是由于研究人群的临床或遗传异质性或方法学偏倚造成的。此外，当外部因素如病毒发挥作用时，这些因素在不同人群中可能不同，导致各种关联。然而，必须考虑到在不同人群中存在许多具有不同频率的分子HLA-A2亚型。因此，进一步的研究应包括HLA-A2亚型的分子分型。
In the elderly, the most common cause of dementia is Alzheimer disease (AD), which is responsible for the age-related progressive neurodegenerative inflammatory condition mediated by the disease. It has been seen that several genetic and environmental factors are involved in AD onset. Epidemiologic data suggest that some genetic determinants of AD might reside in those polymorphisms that regulate immune inflammatory responses, such as the major histocompatibility complex (MHC). Therefore, several MHC polymorphisms have been in the spotlight of a large number of AD association studies. A possible association of HLA-A2 allele with increased susceptibility to AD has been the subject of debate for more than 20 years, even if the results of these studies, in the various populations, are discordant. Thus, to gain insight in this matter, the authors have studied the HLA-A2 allele for a possible association with sporadic AD in a homogeneous population of Italian patients. For this reason, the distribution of HLA-A2 allele in patients with sporadic AD and controls was analyzed by PCR-SSP assay. The results demonstrated a significant difference in the frequency of HLA-A2 allele between patients with sporadic AD and controls (46% versus 38%). Thus, these data confirm a positive role of HLA-A2 allele in the risk of developing AD. However, some of the observed discrepancies may result from clinical or genetic heterogeneity of the populations under study or methodologic biases. Besides, whenever external agents such as viruses play a role, these might different in the various populations leading to various associations. However, it has to be taken into account that there are many molecular HLA-A2 subtypes with different frequencies in various populations. Therefore, further studies should include molecular typing of HLA-A2 subtypes.