Meta-analysis of PvuII, XbaI variants in ESR1 gene and the risk of Alzheimer's disease: The regional European difference

• We conducted a meta-analysis on ESR1 polymorphisms with the risk of AD under different genetic models.
• The PvuII variant, but not XbaI polymorphism, was associated with AD in Caucasians.
• The regional European difference was found in the PvuII polymorphism in AD.
• No relationships were found for the ESR1 polymorphisms and AD risk in Asians.

The PvuII and XbaI polymorphisms of ESR1 gene have been reported in the Alzheimer's disease (AD) studies. However, whether these ESR1 genetic variants can contribute to the risk of AD remains controversial. Herein, we conducted a meta-analysis to clarify the association between ESR1 polymorphisms and the occurrence of AD. Articles were identified by systematic searches in PubMed, Google scholar and Wan Fang Med Online database. The combined odds ratios (OR) and 95% confidence intervals (CI) were calculated within different inherited models. Publication bias tests, subgroup analyses and sensitive analyses were also performed. Overall, the PvuII variant was negatively associated with AD in the Caucasian population (pp vs PP+Pp, OR 0.86, 95%CI (0.76, 0.96)). However, there was a poor association between XbaI polymorphism and AD in European populations. In particular, PvuII variant was found significantly associated with a decreased AD risk in South European samples (pp vs PP+Pp, OR 0.86, 95%CI (0.75, 0.98)). This meta-analysis indicated that regional European differences of ESR1 PvuII polymorphism in the association with the occurrence of AD, which need to be further identified, especially in South European countries.