Association of estrogen receptor alpha gene polymorphism with age at onset, general psychopathology symptoms, and therapeutic effect of schizophrenia

Abstract

BackgroundEstrogen is believed to play an important role in the central nervous system (CNS) and exert a protective role against schizophrenia. Estrogen receptor alpha (ESRα) mediates the biological action of estrogen. Rs2234693 and rs9340799, single nucleotide polymorphisms of ESRα, may be related to many psychiatric disorders, while their association with schizophrenia has not been clarified.MethodsGenotypes rs2234693 and rs9340799 were detected in 303 schizophrenic patients and 292 healthy controls in a Chinese population. The positive and negative syndrome scale (PANSS) was used to estimate symptoms and therapeutic effects. The association of these polymorphisms with schizophrenia and clinical characteristics was analyzed by the chi-square test, analysis of variance, and others.ResultsThe distribution of genotypes and allele frequencies of rs2234693 and rs9340799 exhibited no significant differences between patients and controls, while haplotypes consisting of these polymorphisms had significant differences. For 2234693, T-allele carriers had an earlier age at onset. CC-homozygote carriers had a higher general psychopathology score and its percentage reduction in male and paranoid patients, respectively. CC-homozygote carriers had a higher tension (G4) and poor impulse control (G14) score, mainly in paranoid patients. Furthermore, patients with the CC homozygote had higher reductions of G4 and G14 scores when treated by aripirazole and risperidone, respectively.ConclusionsHaplotypes consisting of these two polymorphisms in ESRα may be strongly associated with schizophrenia. The rs2234693 was related to age at onset, general psychopathology, G4 and G14 symptoms, even the therapeutic effect in different groups.

Gender differences in patients with first‐episode psychosis in the Singapore Early Psychosis Intervention Programme

“…Women may also have a greater buildup of antipsychotics due to their better storing of lipophilic antipsychotics . Combined with the arguably protective factor of oestrogen on schizophrenia, these factors may be the key in explaining the gender differences in the FEP course of illness, but data were not available for analyses. However, many of the commonly explored variables were included in the analysis and are discussed in comparison with findings in the previous literature and their implications for future treatment.…”

Association of MicroRNA137 Gene Polymorphisms with Age at Onset and Positive Symptoms of Schizophrenia in a Han Chinese Population

“…The Kaplan-Meier method and the log-rank test for analysis of survival were used to examine the association of age at onset with genotype [30,31]. The relationships between genotype and clinical variables were tested using student's t-tests.…”

“…All data including sample characteristics, age at onset, baseline symptoms, and therapeutic effect scores were expressed as mean ± SD. The Bonferroni correction was applied to avoid a type I error in the multiple tests [31]. All statistical tests were two-tailed, and P < 0.05 was the threshold level for statistical significance.…”

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits

“…Multiple non-coding ESR1 variants have been implicated as candidates affecting mRNA levels (expression quantitative trait loci; eQTLs) [13] and behavioral traits [1, 6–9, 22–28]. (Table A in S1 File).…”