Abstract：
Alzheimer\'s disease is a neurodegenerative disorder with polygenic etiology. Genetic risk variants for Alzheimer\'s disease differ among populations. Thus, discovering them in each population is clinically important. A total of 118 patients and 97 controls for VDR rs11568820 and 88 patients and 100 healthy controls for MTHFR C677T polymorphism were genotyped to evaluate the association of these polymorphisms with late-onset Alzheimer\'s disease in the Iranian population, along with their impacts on the response to Rivastigmine treatment. The VDR C allele was significantly associated with Alzheimer\'s disease and provided protection against it (P = 0.003, RR = 1.14, 95% CI 1.04-1.24), while the T allele increased susceptibility (P = 0.003, RR = 1.93, 95% CI 1.23-3.02). These results were also considerable upon excluding the effect of APOE ε4 allele. The Prevalence-corrected Positive Predictive Value was 1.71% for the VDR CC genotype and 4% for the VDR CT genotype, indicating lower and almost twofold higher chances of developing Alzheimer\'s disease, respectively. No significant correlation was observed between MTHFR C677T and Alzheimer\'s disease. Based on our pharmacogenetic study, MTHFR T allele carriers lacking APOE ε4 allele showed a better response to Rivastigmine treatment after a 2-year follow-up. Moreover, patients with VDR CC genotype displayed milder Alzheimer\'s disease, particularly when coincided with the APOE ε4 allele. The VDR rs11568820 polymorphism affects both Alzheimer\'s disease risk and the response to Rivastigmine in Iranian patients. Also, MTHFR C677T polymorphism may play a role in the response to Rivastigmine, through a pathway that needs to be elucidated in future studies.
摘要：
阿尔茨海默病是一种多基因病因的神经退行性疾病。阿尔茨海默病的遗传风险变异在人群中不同。因此，在每个人群中发现它们在临床上很重要。共有118名患者和97名VDRrs11568820和88名患者和100名健康对照的MTHFRC677T多态性进行了基因分型，以评估这些多态性与伊朗人群迟发性阿尔茨海默病的关联。以及它们对Rivastigmine治疗反应的影响。VDRC等位基因与阿尔茨海默病显著相关并对其提供保护(P=0.003,RR=1.14,95%CI1.04-1.24),而T等位基因易感性增加(P=0.003,RR=1.93,95%CI1.23-3.02)。这些结果在排除APOEε4等位基因的影响时也是相当大的。VDRCC基因型的患病率校正阳性预测值为1.71％，VDRCT基因型为4％，表明患阿尔茨海默病的机率较低，几乎高两倍，分别。MTHFRC677T与阿尔茨海默病无显著相关性。根据我们的药物遗传学研究，缺乏APOEε4等位基因的MTHFRT等位基因携带者在2年的随访后对Rivastigmine治疗表现出更好的反应。此外，VDRCC基因型患者表现出轻度阿尔茨海默病，特别是当与APOEε4等位基因重合时。VDRrs11568820多态性影响伊朗患者的阿尔茨海默病风险和对卡巴拉汀的反应。此外，MTHFRC677T多态性可能在利瓦斯的明的反应中起作用，通过一条需要在未来研究中阐明的途径。
