Association of Estrogen Receptor 1 (ESR1) PvuII and XbaI polymorphisms and peripheral ESR1 mRNA levels with Alzheimer's disease

Abstract Objectives Estrogen receptor 1 (ESR1) gene polymorphisms are associated with Alzheimer's disease (AD) and ESR1 mRNA transcription is affected by polymorphisms in the first intronic region of the gene. ESR1 PvuII rs2234693 (NM 000125.3:c.453-397T > C) and XbaI rs9340799 (NM 000125.3:c.453-351A > G) polymorphisms have been shown to be associated with AD. In this study, we sought to determine the association of PvuII and XbaI polymorphisms with AD. We also examined whether PvuII and XbaI polymorphisms affect disease susceptibility by influencing ESR1 mRNA expression. Methods Genotyping was performed in 424 AD patients and 302 controls. The polymerase chain reaction and restriction enzyme digestion was used to determine the prevalence of the ESR1 polymorphisms. ESR1 mRNA expression was analyzed in blood cells of 85 patients and 53 age-matched controls by quantitative real-time polymerase chain reaction. Results Our results showed no significant difference in genotype and allele frequencies of ESR1 PvuII and XbaI polymorphisms between patients and controls but frequencies of the PvuII C and XbaI G alleles were significantly higher in patients with the APOE ε4 allele. ESR1 mRNA levels were significantly lower in AD patients compared with controls (p = 0.001). XbaI A allele is significantly associated with lower ESR1 mRNA levels (p = 0.044) and this association remained significant after adjusting for age, gender and APOE ε4 carrier status (p = 0.035). Conclusion Our study showed that the distribution of PvuII and XbaI alleles were associated with the APOE ε4 allele. The XbaI polymorphism may be associated with a higher risk of AD by altering ESR1 mRNA levels.