Abstract
Evidences have been gathered from several studies suggest that a mechanism involving an estrogen-signaling pathway may contribute to modulate risk for Alzheimer?s disease. It was demonstrated that estrogen up-regulates the expression of apolipoprotein E gene, which has a role in the metabolism of b-amyloid that is related to the progress of Alzheimer?s disease. Case-control studies have found an increased frequency of PvuII and XbaI polymorphisms in affected subjects. In this study we explore the possible association of different polymorphic forms of human a-estrogen receptor (ER- a) with the risk to late onset Alzheimer?s disease in north-west Iranian population. We conducted a case-control study in a dataset of 160 LOAD patients and 163 healthy controls that have been matched in gender and age. To evaluate the PvuII and XbaI polymorphisms in Alzheimer?s disease we used PCR/RFLP method and genotype frequencies were statistically determined. The PCR products prepared from 21 AD cases and 20 healthy controls were randomly purified by ethanol precipitation and bidirectionally sequenced. The frequency of normal and mutated alleles for PvuII and XbaI locuses respectively, in the LOAD group were significantly higher than those in the control group (P<0.001, OR=0.51, 95 % CI 0.35-0.74 for XbaI locus; P<0.001, OR=0.41, 95 % CI 0.3-0.57 for PvuII locus). This result suggests that ER? XbaI and PvuII polymorphism is an additional risk factor for late-onset Alzheimer?s disease.
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