Bi Xiu-Hua, Zhao Hua-Lu, Zhang Zhen-Xin, Zhang Jun-Wu
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
Neurobiol Aging. 2009 Oct;30(10):1601-7. doi: 10.1016/j.neurobiolaging.2007.12.010. Epub 2008 Feb 6.
We examined polymorphisms in reduced folate carrier gene (RFC1) and methylenetetrahydrofolate reductase gene (MTHFR) for association with sporadic AD (SAD) in Chinese population. Significant associations of RFC1 A80G G allele and GG genotype with SAD (p=0.008, OR=1.312, 95%CI=1.072-1.605, and p=0.042, OR=1.383, 95%CI=1.012-1.890) were found. Further stratification of total samples by APOE epsilon4 carrier status, age/age at onset and gender revealed that RFC1 A80G G allele was an APOE epsilon4-independent risk factor for late-onset AD, and it might increase the risk of AD in females. No significant associations of MTHFR C677T allele and genotype with AD were observed in total samples, but significant associations of T allele and TT genotype with AD (p=0.031, OR=1.586, 95%CI=1.042-2.414, and p=0.028, OR=2.250, 95%CI=1.074-4.712) were identified in APOE epsilon4 carrier subgroup, suggesting that MTHFR 677 T allele and APOE epsilon4 allele may synergistically act to increase AD risk. No significant effect of RFC1 G80A and MTHFR C677T polymorphisms on plasma folate and homocysteine levels was detected.
我们检测了中国人群中还原型叶酸载体基因（RFC1）和亚甲基四氢叶酸还原酶基因（MTHFR）的多态性与散发性阿尔茨海默病（SAD）的相关性。发现RFC1 A80G的G等位基因和GG基因型与SAD存在显著相关性（p = 0.008，OR = 1.312，95%CI = 1.072 - 1.605；以及p = 0.042，OR = 1.383，95%CI = 1.012 - 1.890）。根据APOE ε4携带者状态、发病年龄/年龄和性别对总样本进行进一步分层分析显示，RFC1 A80G的G等位基因是晚发性AD的一个不依赖APOE ε4的危险因素，且可能增加女性患AD的风险。在总样本中未观察到MTHFR C677T等位基因和基因型与AD有显著相关性，但在APOE ε4携带者亚组中发现T等位基因和TT基因型与AD存在显著相关性（p = 0.031，OR = 1.586，95%CI = 1.042 - 2.414；以及p = 0.028，OR = 2.250，95%CI = 1.074 - 4.712），这表明MTHFR 677 T等位基因和APOE ε4等位基因可能协同作用增加AD风险。未检测到RFC1 G80A和MTHFR C677T多态性对血浆叶酸和同型半胱氨酸水平有显著影响。
