Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China.
Int J Geriatr Psychiatry. 2009 Sep;24(9):921-6. doi: 10.1002/gps.2196.
We previously found that the polymorphisms of cholesterol 24-hydroxylase (CYP46A1) gene were associated with the risk of Alzheimer's disease (AD) in Chinese. However, its effect in predicting progression of cognitive decline remains unknown.
Two hundred and eighty-one Chinese subjects (121 cognitively intact, 101 with mild cognitive impairment and 59 with mildly dementia) were followed-up with a mean (SD) duration of 25.22(5.74) months. Association between the CYP46A1 gene polymorphisms and 2-year cognitive deterioration were evaluated.
At follow-up, 225(80.0%) subjects were reassessed. Sixty-three subjects were diagnosed as AD, 68 were MCI and 94 were cognitively intact. Among them, 158 had improved or remained stable while 67 deteriorated. The 'deteriorated' group was older than 'improved or stable' group (t-test, t = -2.87, p < 0.001). IVS2-150 polymorphism was associated with a higher risk of cognitive deterioration. Subjects with T allele were more likely to deteriorate compared with those without T allele (Pearson chi(2) = 8.98, df 2, p = 0.011). IVS3-128 CC genotype was higher in 'improved or stable' group (Likelihood Ratio = 6.55, df 2, p = 0.038), suggesting a protective role for this allele. The two other polymorphisms, IVS1-192 and IVS4-122, did not show any significant association with cognitive function.
CYP46A1 gene may act to modulate the course of cognitive deterioration in late life.
我们之前发现胆固醇 24-羟化酶（CYP46A1）基因的多态性与中国人患阿尔茨海默病（AD）的风险相关。然而，其在预测认知能力下降进展方面的作用尚不清楚。
281 名中国受试者（121 名认知正常、101 名轻度认知障碍和 59 名轻度痴呆）进行了平均（SD）25.22（5.74）个月的随访。评估 CYP46A1 基因多态性与 2 年认知恶化的关系。
随访时，225 名（80.0%）受试者重新评估。63 名被诊断为 AD，68 名 MCI，94 名认知正常。其中，158 名改善或稳定，67 名恶化。与“改善或稳定”组相比，“恶化”组年龄更大（t 检验，t=-2.87，p<0.001）。IVS2-150 多态性与认知恶化的风险增加相关。与无 T 等位基因者相比，携带 T 等位基因者更有可能恶化（Pearson chi(2)=8.98，df 2，p=0.011）。IVS3-128CC 基因型在“改善或稳定”组中更高（似然比=6.55，df 2，p=0.038），表明该等位基因具有保护作用。另外两个多态性 IVS1-192 和 IVS4-122 与认知功能无显著相关性。
CYP46A1 基因可能影响晚年认知恶化的进程。
