Listì Florinda, Candore Giuseppina, Balistreri Carmela Rita, Grimaldi Maria Paola, Orlando Valentina, Vasto Sonya, Colonna-Romano Giuseppina, Lio Domenico, Licastro Federico, Franceschi Claudio, Caruso Calogero
Immunosenescence Unit, Department of Pathobiology and Biomedical Methodology, University of Palermo, Palermo, Italy.
Rejuvenation Res. 2006 Spring;9(1):99-101. doi: 10.1089/rej.2006.9.99.
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.
在老年人中，痴呆最常见的病因是阿尔茨海默病（AD），它是由该疾病介导的与年龄相关的进行性神经退行性炎症性疾病。已经发现，AD的发病涉及多种遗传和环境因素。流行病学数据表明，AD的一些遗传决定因素可能存在于调节免疫炎症反应的多态性中，例如主要组织相容性复合体（MHC）。因此，几种MHC多态性一直是大量AD关联研究的焦点。HLA - A2等位基因与AD易感性增加之间的可能关联已经成为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，为了深入了解此事，作者在一组同质的意大利患者中研究了HLA - A2等位基因与散发性AD的可能关联。为此，通过PCR - SSP分析检测散发性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患者和对照组之间HLA - A2等位基因频率存在显著差异（46%对38%）。因此，这些数据证实了HLA - A2等位基因在AD发病风险中的积极作用。然而，观察到的一些差异可能是由于所研究人群的临床或遗传异质性或方法学偏差导致的。此外，每当病毒等外部因素起作用时，这些因素在不同人群中可能不同，从而导致不同的关联。然而，必须考虑到在不同人群中存在许多频率不同的分子HLA - A2亚型。因此，进一步的研究应包括HLA - A2亚型的分子分型。
