Orlacchio Antonio, Kawarai Toshitaka, Polidoro Mario, Stefani Alessandro, Orlacchio Aldo, St George-Hyslop Peter H, Bernardi Giorgio
Laboratorio di Neurogenetica, IRCCS Santa Lucia, Via Ardeatina 354, 00179, Rome, Italy.
Neurosci Lett. 2002 Nov 22;333(2):115-8. doi: 10.1016/s0304-3940(02)01022-4.
The biological study of the Nicastrin protein shows its crucial role in the pathogenesis of Alzheimer's disease (AD). We tested the hypothesis that the Nicastrin (NCSTN) gene might be genetically associated with AD. The association analysis of two single nucleotide polymorphisms (SNPs) in the coding region (cSNPs) of NCSTN were performed in an Italian population. No evidence of association was obtained between the two SNPs investigated in sporadic and familial AD cases under the stratification of currently known genetic risk factors including the apolipoprotein E (APOE), the presenilins and the beta-amyloid precursor protein. The result suggests no apparent synergic interaction between the NCSTN and APOE epsilon 4 in the risk to develop the late onset sporadic form of AD. But considering its biological effects, the result can not exclude the NCSTN as candidate for genetic factor in AD. Further genetic study of the NCSTN would be necessary to evaluate the potential genetic involvement in AD.
对尼卡斯特林蛋白的生物学研究表明其在阿尔茨海默病（AD）发病机制中起关键作用。我们检验了尼卡斯特林（NCSTN）基因可能与AD存在遗传关联的假说。在意大利人群中对NCSTN编码区的两个单核苷酸多态性（SNP）进行了关联分析。在包括载脂蛋白E（APOE）、早老素和β淀粉样前体蛋白等当前已知遗传风险因素分层的散发性和家族性AD病例中，未发现所研究的两个SNP之间存在关联证据。结果表明，在晚发型散发性AD发病风险中，NCSTN与APOE ε4之间无明显协同相互作用。但考虑到其生物学效应，该结果不能排除NCSTN作为AD遗传因素候选者的可能性。有必要对NCSTN进行进一步的遗传学研究，以评估其在AD中潜在的遗传作用。
