Positive association between an estrogen receptor gene polymorphism and Parkinson's disease with dementia

Abstract

Parkinson's disease (PD) is a common cause of dementia in the elderly. Dementia in Alzheimer's disease (AD) and PD share common biologic and clinical features. The estrogen receptor (ER) gene is one of the susceptibility genes for AD. In order to test the hypothesis that the overlap between AD and PD may have a genetic basis, we determined ER gene polymorphisms in 13 PD patients with dementia (PDD) (age ± SD; 71.9 ± 5.5 years), 71 PD patients without dementia (PDND) (68.4 ± 7.5 years), 86 AD patients (76.8 ± 8.0 years) and 51 control subjects (CTL) (74.9 ± 6.9 years). ER genotypes were classified as a P or p allele on the basis of a Pvu II‐RFLP, and X and x on the basis of a Xba I‐RFLP. The frequency of the P allele in the PDD group as well as the AD group was higher than that in CTL. There was no significant difference in the distribution of the P allele between CTL and PDND. There were no significant differences in the distribution of the X allele among the PDD, PDND and CTL groups, whereas a higher incidence was found in AD. We conclude that the ER gene may be a common susceptibility gene for dementia in PD as well as AD.

Estrogen receptor polymorphisms and incident dementia: The prospective 3C study

“…The direction of these associations is supported by a majority of significant case-control studies [8][9][10][11]37], although several prior studies have reported larger effect sizes in smaller samples. These differences may be partly explained by the populations studied, as the majority of significant findings have been found in Japanese populations [10,11,37].…”

“…These differences may be partly explained by the populations studied, as the majority of significant findings have been found in Japanese populations [10,11,37]. Although these ESR1genotype frequencies are relatively similar between Caucasian and Asian populations, ethnic differences in linkage disequilibrium between these polymorphisms and other functional polymorphisms is highly likely [38].…”

“…Some of these studies have reported that AD patients had a significantly higher frequency of the minor C and G alleles of rs2234693 and rs9340799 respectively [8][9][10][11], yet other studies have found no significant associations [12][13][14] or even reverse associations [15,16]. Meta-analyses conducted a few years ago found a small but significant association between the minor alleles of these polymorphisms and an increased risk of AD (OR~1.2) [17,18], however this is not supported by the most recent metaanalysis on the Alzheimer's Research Forum (http://www.alzgene.org).…”

Allelic variation investigation of the estrogen receptor within an Australian multiple sclerosis population

“…Studies on animal models have shown estradiol (E2) dose dependent inhibition of clinical signs of EAE when E2 was given a week before EAE induction [18] and [19]. Also of interest, several positive association results have been found between estrogen receptor variants and other autoimmune disorders including lupus and rheumatoid arthritis [20] and [21] as well as with the Parkinson neurodegenerative disease [22]. In addition, an association has also been found between the PvuII ESR1 polymorphism and the HLA DR2 allele [15] and a recent Japanese study found an independent positive association of the ESR1 PvuII T allele with HLA-DRB1 1511 allele, an allele associated with MS development [23].…”

Are gonadal steroid hormones involved in disorders of brain aging?

“…For example, the frequency of specific oestrogen receptor alpha gene polymorphisms is higher in women with dementia (Isoe-Wada et al ., 1999;Mattila et al ., 2000). Moreover, the risk of Alzheimer's disease has been calculated to be seven-fold greater in individuals that are homozygous for both the apolipoprotein E allele, apoE epsilon 4, and the oestrogen receptor alpha allelle ER α PPXX (Brandi et al ., 1999;Isoe-Wada et al ., 1999).…”