Study of estrogen receptors polymorphisms in women with Takotsubo cardiomyopathy or myocardial infarction

Purpose: Takotsubo cardiomyopathy (TKCM) has a higher prevalence in females and primarily affects menopausal age when estrogen levels are particularly low. Cohort studies suggest an association between polymorphisms of ESR1 and ESR2 genes and myocardial infarction (MI), but data are lacking about the role of the estrogen receptor genes in TKCM. Methods: Two polymorphisms of ESR1 gene (–397 T>C rs2234693, –351 A>G rs9340799), and ESR2 gene (–1839 G>T rs1271572 and 1082 G>A rs1256049), with their associated haplotypes, were evaluated in 18 women affected by TKCM (70±6.9 yrs), 50 women with myocardial infarction (76±9 yrs) and 30 healthy controls (66±3.4 yrs). Results: Homozygous for T in ESR1 –397 was found prevailing in patients with TKCM (Table 1). As to haplotypes of ESR genes, we observed a higher prevalence of haplotypes T in patients with TKCM both in ESR1 –397 and ESR2 –1839 (Table 2). On logistic regression analysis the haplotype T of ESR1 –397 was significantly associated with TKCM, whereas the haplotypes G for ESR1 –351 and for ESR2 –1839, respectively, were associated with MI (Table 3). Table 1. Pearson’s chi square – ESR1 -397 T>C TT CT CC Controls 32.4% 47.1% 20.6% Takotsubo 61.1% 38.9% 0% Myocardial Infarction 26.2% 61.9% 11.9% p=0.04 Table 2. Pearson’s chi square – Polymorphisms ESR1 -397 ESR1 -351 ESR2 -1082 ESR2 -1839 Haplotype T C A G G A T G Controls 55.9% 44.1% 59.7% 40.3% 52.9% 47.1% 50.1% 49.9% Takotsubo 80.6% 19.4% 55.9% 44.1% 55.6% 44.4% 61.1% 39.9% Myocardial Infarction 57.1% 42.9% 42.1% 57.9% 58.3% 41.7% 28.6% 71.4% p 0.029 NS NS 0.001 Table 3. Simple logistic regression analysis polymorphisms Takotsubo Myocardial Infarction OR (CI 95%) p OR (CI 95%) p ESR1 –397 T 3.27 (1.26–8.49) 0.015 0.95 (0.49–1.81) 0.87 ESR1 –351 G 0.85 (0.37–1.99) 0.71 2.03 (1.02–4.02) 0.04 ESR2 –1082 G 1.11 (0.49–2.50) 0.79 1.24 (0.65–2.37) 0.5 ESR2 –1839 G 1.57 (0.68–3.60) 0.28 2.5 (1.26–4.94) 0.008