The Relation Of ER Gene And Apoliporotein E Gene Polymorphisms With Age At Natural Menopause And Menopausal Syndromes

Objective To investigate the role of estrogen receptor(ER) and apolipoprotein E(apoE) gene in age at natural menopause and menopausal syndromes.Methods The ER genotype (PvuII and XbaI sites) and apoE genotype were assessed by PCR-RFLP in 189 postmenopausal women. An unified questionnaire was completed including the age at natural menopause and menopausal syndromes. The effect of estrogen receptor(ER) and apoE genotype on age at natural menopause and menopausal syndromes were analyzed.Results 1. The P allele frequency was 0.42, and the p allele frequency was 0.58. The X allele frequency was 0.21, and the x allele frequency was 0.79. The allele frequency of apoE was as follows: 2, 0.08;3, 0.83; 4, 0.09. 2. One-way ANOVA revealed significant ER- genotypic effects (P = 0.046) for the age at natural menopause. The mean the age at natural menopause were earlier in women with the pp genotype compared to those with PP genotype (P = 0.013), whereas there was no significant differences between ER Xba I polymorphism and the mean the age at natural menopause (P=0.405). There was significant difference in the mean age at menopause among the frequent allele combination 2/3, 3/3, 3/4(P=0.005). In group 3/3, the mean age at menopause were earlier than those in group 3/4 (.P=0.001). 3. The mean age at menopause was earliest in group ppE3/3 than other groups (P=0.009). Split file analyses showed that there was a significant association between ER polymorphism and menopausal age in the apoE 3/3 women (P=0.048). 4. The genotype distributions of these RFLPs were not differ between symptomatic and asymptomatic women(P=0.410,0.571,0.284 respectively). There were no statistically significant differences between genotypes and menopausal symptoms such as hot flash, mental symptoms. 5. Multiple regression analyses revealed that age at natural menopause had correlation with menstrual periods, breast feed, apoE and ER gene (P=0.033, 0.014, 0.003, 0.02 respectively). There was a significant association between irregular menstrual cycles prior to stopping menstruation and menopausal symptoms (P=0.025). There was a significant association between irregular menstrual cycles and occurrenceprior to stopping menstruation and mental symptoms. (P=0.026, 0.049 respectively).Conclusion 1. ER gene and apoE gene are associated with the age at natural menopause, and indicate some degree of interaction between the effects of the ER and apoE genes leading to significant variations in the age at natural menopause. 2. There might be no correlation between menopausal symptoms and the ER or apoE gene. 3. Environmental and lifestyle factors have been found to influence menopausal age and menopausal symptoms.