Key Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
J Clin Neurosci. 2010 Jun;17(6):766-9. doi: 10.1016/j.jocn.2009.10.017. Epub 2010 Apr 8.
Both invitro and invivo alpha-1-antichymotrypsin (ACT) directly inhibits amyloid beta peptide (Abeta) degradation and promotes Abeta deposition. However, whether the genetic variants in the regulatory region (including the promoter and the two enhancers) of the ACT gene affect susceptibility to Alzheimer's disease (AD) remains controversial. Here, we screened ACT promoter and enhancers in 244 patients with sporadic Alzheimer's disease (SAD) and 205 control patients, both of north Han-Chinese origin. Four single nucleotide polymorphisms (SNP) were found: (i) 11510T/C (rs10145747, named as ACT1); 11496G/A (rs4375593, ACT2); (iii) 11491T/C (rs4508366, ACT3); and (iv) 51G/T (rs1884082, ACT4). Neither individual SNP nor haplotypes were associated with AD onset. We concluded that the effect of the variations in the ACT regulatory region must be very limited, if occurring at all.
无论是在体外还是体内，α-1-抗胰蛋白酶 (ACT) 都直接抑制淀粉样β肽 (Abeta) 的降解并促进 Abeta 的沉积。然而，ACT 基因调节区（包括启动子和两个增强子）的遗传变异是否会影响阿尔茨海默病（AD）的易感性仍存在争议。在此，我们在 244 例散发性阿尔茨海默病（SAD）患者和 205 例汉族对照患者中筛选了 ACT 启动子和增强子。发现了四个单核苷酸多态性（SNP）：（i）11510T/C（rs10145747，命名为 ACT1）；11496G/A（rs4375593，ACT2）；（iii）11491T/C（rs4508366，ACT3）；和（iv）51G/T（rs1884082，ACT4）。没有单个 SNP 或单倍型与 AD 发病相关。我们得出结论，如果确实存在的话，ACT 调节区变异的影响一定非常有限。
