Association between ESR1 and ESR2 gene polymorphisms and hyperlipidemia in Chinese Han postmenopausal women

Abstract

Estrogen was considered to be an important protective factor for cardiovascular diseases in women. Genetic association studies suggested that variations of ESR1 and ESR2 genes might have a potential role in lipid profile. Our study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) of ESR1 and ESR2 with hyperlipidemia in Chinese Han postmenopausal women. A total of 443 postmenopausal women aged between 55 and 71 years were recruited from Shanghai, China for a casecontrol study (154 women with hyperlipidemia and 289 controls). We measured plasma estradiol concentration, glucose and lipid profile levels, evaluated their lifestyle and sequenced four SNPs, namely PvuII (rs2234693) and XbaI (rs9340799) of ESR1 and 1082A4G (rs1256049) and 1730A4G (rs4986938) of ESR2. PvuII (rs2234693) and XbaI (rs9340799) showed significantly different distributions between cases and controls (P¼0.002 and P¼0.023, respectively). In addition, haplotypes constructed from PvuII-XbaI were also associated with hyperlipidemia (global P¼0.012). Haplotypes T-A (P¼0.005, odds ratio (OR) 1.52, 95% confidence interval (95% CI): 1.13-2.05) and C-G (P¼0.010, OR 0.62, 95% CI: 0.43-0.89) had susceptible and protective effects, respectively. 1082A4G (rs1256049) and 1730A4G (rs4986938) showed no statistical association with hyperlipidemia. In conclusion, our results suggested that ESR1 might have a potential role in hyperlipidemia risk, independent of age, estradiol level, body mass index and lifestyle in Chinese Han postmenopausal women.

Are polymorphisms in oestrogen receptors genes associated with lipid levels in response to hormone therapy?

“…A few association studies between ESR1 and ESR2 gene polymorphisms and lipid levels in response to HT have been published previously [13,20,22,24]. However, to the best of our knowledge, no study has investigated this particular SNP set for HT-dependent effects on lipid levels in postmenopausal women.…”

“…Silvestri et al [26] detected an association between the *G allele of rs4986938 and lower T-chol in HT+ postmenopausal women, while Saltiki et al [27] identified a link between the *A allele of rs4986938 and enhanced CVD risk in postmenopausal women. Zhao et al [22] and Almeida et al [24] did not observe an association of the rs4986938 polymorphism with a specific lipid profile.…”

“…The *A allele of rs1256049 is associated with lower total cholesterol (T-chol) and LDL-C levels in HT+ postmenopausal women [24] and with atherosclerosis in young adults from Finland [25]. However, Zhao et al [22] did not observe an association of rs1256049 with hyperlipidaemia in Chinese Han postmenopausal women. Silvestri et al [26] detected an association between the *G allele of rs4986938 and lower T-chol in HT+ postmenopausal women, while Saltiki et al [27] identified a link between the *A allele of rs4986938 and enhanced CVD risk in postmenopausal women.…”

“…The *C allele of the rs2234693 polymorphism was shown to be associated with a cardioprotective profile [14,20], while in other studies, this same allele was also shown to be associated with increased risk and severity of CVD [12,16,17]. The *T allele of the same polymorphism has also been linked to a cardioprotective profile [13,19] and to an increased risk of hyperlipidaemia [22]. In our previous study [23], this polymorphism was not associated with changes in lipid profile in either postmenopausal women who were HT users (HT+) or postmenopausal HT nonusers (HT−).…”

“…In a review of the literature, we identified several studies that investigated the association of ESR1 gene polymorphisms with intermediate or endpoint markers of CVD, as lipid levels [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Most of these studies focused on two polymorphisms, rs2234693 and rs9340799.…”