Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan, Italy.
Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):991-9. doi: 10.1177/039463200902200414.
In this study, the distribution of HLA-A alleles was analyzed in Italian Alzheimer's Disease (AD)patients. Interaction between HLA alleles, APOE genotypes, age of onset, and gender were also analyzed. The results were compared to those obtained in healthy controls (HC). One hundred-seventy-three AD patients and 258 age-and-sex-matched healthy controls were enrolled in the study. AD patients were classified according to age at the onset of disease using quartiles of the distribution. HLA-A genotyping was performed by PCR-SSP; APOE genotyping was performed by RFLP. A correlation between late disease onset and HLA-A01 was observed. Thus, HLA-A01, calculated as number of alleles, was significantly more present in patients with age of onset > 74.0 years than in HC (20% vs 10.5%; p=0.014); the distribution of this allele was skewed also in patients 68.1-74 years of age (16.3%), even if the difference did not reach statistical significance. The relative risk ratio (RRR) of AD onset calculated by a multinomial logistic regression adjusted for sex and presence of APOE-4 confirmed a significant association of HLA-A01 with AD onset > 74.0 years of age (RRR=2.2; 95%CI: 1.1-4.6; p=0.033). A high RRR (2.04) was also present in patients 68.1-74 years (p=0.064). Lower age of disease onset did not correlate with HLA-A01. Data herein suggest that the presence of HLA-A*01 results in delayed AD development, even in patients carrying APOE-4. These results could offer new insights into the etiopathogenesis of Alzheimer's disease.
在这项研究中，分析了意大利阿尔茨海默病（AD）患者中 HLA-A 等位基因的分布。还分析了 HLA 等位基因、APOE 基因型、发病年龄和性别之间的相互作用。将这些结果与健康对照组（HC）的结果进行了比较。该研究纳入了 173 名 AD 患者和 258 名年龄和性别匹配的健康对照者。根据疾病发病年龄的四分位数，将 AD 患者进行分类。通过 PCR-SSP 进行 HLA-A 基因分型；通过 RFLP 进行 APOE 基因分型。观察到晚发性疾病与 HLA-A01 之间存在相关性。因此，计算出的 HLA-A01 等位基因数量在发病年龄>74 岁的患者中明显多于 HC（20%比 10.5%；p=0.014）；在 68.1-74 岁的患者中，该等位基因的分布也存在偏倚（16.3%），尽管差异没有达到统计学意义。通过调整性别和 APOE-4 存在的多项逻辑回归计算的 AD 发病相对风险比（RRR）证实，HLA-A01 与发病年龄>74 岁的 AD 发病显著相关（RRR=2.2；95%CI：1.1-4.6；p=0.033）。在 68.1-74 岁的患者中，RRR 也较高（2.04；p=0.064）。发病年龄较低与 HLA-A01 无关。本研究数据表明，HLA-A*01 的存在导致 AD 发病延迟，即使在携带 APOE-4 的患者中也是如此。这些结果可以为阿尔茨海默病的病因发病机制提供新的见解。
