Association of estrogen receptor 1 (ESR1) haplotypes with risk for systemic lupus erythematosus among South Indians.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving genetic, epigenetic and environmental factors and has higher incidence in women. In this study, we explored the association of estrogen receptor 1 (ESR1) rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms with susceptibility to SLE. PCR-RFLP and ELISA were used for genetic analysis and determination of specific autoantibodies, respectively. The univariate analysis showed no independent association of rs2234693 (OR: 1.14, 95% CI: 0.87 - 1.49, p = 0.36) and rs9340799 (OR: 0.87, 95% CI: 0.66-1.14, p = 0.34). The haplotype analysis using SHEsis platform revealed strong linkage disequilibrium between these two polymorphisms (D': 0.81, r2: 0.55). Among the four haplotype groups, the C-A haplotype (rs2234693-rs9340799) was strongly associated with the risk for SLE (OR: 2.10, 95% CI: 1.32 - 3.34, p = 0.001). The homozygous variant genotype of rs2234693 exhibited elevated TNF-α and depleted IFN-α, while the effects of rs9340799 were contradictory. The wild genotype of rs2234693 exhibited lower levels of IL-12 with number of rs9340799 variant alleles pronouncing this effect. From this study, it is concluded that the ESR1 haplotypes may influence the Th2 cytokine profile and susceptibility to SLE among the South Indians.
Publication Date: 2015-12-17
Journal: Indian journal of experimental biology
ESR1 and ESR2 polymorphisms in the BIG 1-98 trial comparing adjuvant letrozole versus tamoxifen or their sequence for early breast cancer.
Estrogen receptor 1 (ESR1) and ESR2 gene polymorphisms have been associated with endocrine-mediated physiological mechanisms, and inconsistently with breast cancer risk and outcomes, bone mineral density changes, and hot flushes/night sweats. DNA was isolated and genotyped for six ESR1 and two ESR2 single-nucleotide polymorphisms (SNPs) from tumor specimens from 3691 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Associations with recurrence and adverse events (AEs) were assessed using Cox proportional hazards models. 3401 samples were successfully genotyped for five SNPs. ESR1 rs9340799(XbaI) (T>C) variants CC or TC were associated with reduced breast cancer risk (HR = 0.82,95% CI = 0.67-1.0), and ESR1 rs2077647 (T>C) variants CC or TC was associated with reduced distant recurrence risk (HR = 0.69, 95% CI = 0.53-0.90), both regardless of the treatments. No differential treatment effects (letrozole vs. tamoxifen) were observed for the association of outcome with any of the SNPs. Letrozole-treated patients with rs2077647 (T>C) variants CC and TC had a reduced risk of bone AE (HR = 0.75, 95% CI = 0.58-0.98, P interaction = 0.08), whereas patients with rs4986938 (G>A) genotype variants AA and AG had an increased risk of bone AE (HR = 1.37, 95% CI = 1.01-1.84, P interaction = 0.07). We observed that (1) rare ESR1 homozygous polymorphisms were associated with lower recurrence, and (2) ESR1 and ESR2 SNPs were associated with bone AEs in letrozole-treated patients. Genes that are involved in estrogen signaling and synthesis have the potential to affect both breast cancer recurrence and side effects, suggesting that individual treatment strategies can incorporate not only oncogenic drivers but also SNPs related to estrogen activity.
Publication Date: 2015-11-23
Journal: Breast cancer research and treatment
Estrogen Receptor Gene (ESR1) PVUII and XBAI Polymorphisms and Bone Mineral Density in Kazakh Women.
Osteoporosis is a common age-related disease that is strongly influenced by genetics. Polymorphisms of the estrogen receptor gene alpha (ESR1) are consistently been associated with bone mineral density (BMD) and fracture.The purpose of this investigation was to evaluate potential association of single nucleotide polymorphism (SNP) variants of the ESR1 gene and bone mineral density (BMD) of the lumbar spine in Kazakh women.
140 female participants in Pavlodar clinics with varying measures of BMD. We are examined the potential association of BMD with 2 SNPs from the ESR1 gene (rs2234693 [PvuII] and rs9340799 [XbaI]). Genotyping of the PvuII and XbaI polymorphisms was performed by direct sequencing of the gene fragments containing restriction sites with the identification of genotypes PP, Pp, pp and XX, Xx, xx respectively.
Unadjusted mean BMD values ranged from 1.14±0.14 g/cm
The PvuII polymorphism had a weak association with lumbar spine BMD. XbaI polymorphism was unlikely to be a predictor of lumbar spine BMD in Kazakh women. These conclusions could help to determine the genetic risk factors for osteoporosis; however, further studies on the association between gene polymorphisms and BMD are needed including larger numbers of participants and genes to clarify genetic risks.
Publication Date: 2014-01-24
Journal: Central Asian journal of global health
Impact of genetic variants of IL-6, IL6R, LRP5, ESR1 and SP7 genes on bone mineral density in postmenopausal Mexican-Mestizo women with obesity.
Since obesity and osteoporosis present a high genetic predisposition and polymorphisms of IL-6, IL6R, LRP5, ESR1 and SP7 may influence the risk of both diseases, the aim of this study was to analyze the possible association of polymorphisms in these genes, as well as their haplotypes, with BMD variations in postmenopausal Mexican-Mestizo women with grade 2 or grade 3 obesity.
One hundred eighty unrelated postmenopausal women with grade 2 or grade 3 obesity were included. BMD was measured in total hip and lumbar spine by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Rs1800795 of IL-6, rs2228145 of IL6R, rs3736228 of LRP5, rs9340799 (XbaI) and rs2234693 (PvuII), of ESR1, rs10876432 and rs2016266, of SP7 (and their haplotypes), were studied by real-time PCR allelic discrimination. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis was conducted.
Using WHO criteria, 54.5% had grade 2 obesity, and 45.5% had grade 3 obesity. Regarding DXA results, 11.1% women had osteoporosis, 41.7% had osteopenia, and 47.2% had normal BMD. Genotype and haplotype analysis showed no significant differences with BMD variations at the lumbar spine, total hip or femoral neck.
We did not find a significant association between the polymorphisms analyzed or their haplotypes and BMD variations in postmenopausal women with obesity. The higher BMD observed in women with obesity could be the result of an adaptive response to the higher loading of the skeleton.
Publication Date: 2013-07-31