Scalco Renata, Trarbach Ericka, Albuquerque Edoarda Vasco de Albuquerque, Homma Thais Kataoka, Inoue-Lima Thais Hissami, Nishi Mirian Yumie, Mendonca Berenice Bilharinho, Jorge Alexander A L
R Scalco, Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina , Universidade de Sao Paulo, Sao Paulo, 01246-903, Brazil.
E Trarbach, Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina , Universidade de Sao Paulo, Sao Paulo, Brazil.
Endocr Connect. 2019 Nov;8(11):1513-1519. doi: 10.1530/EC-19-0398.
Most patients with Turner syndrome (TS) need hormone replacement therapy because of hypergonadotropic hypogonadism; individual outcomes, however, are highly variable. Our objective was to assess the influence of five estrogen receptor 1 gene (ESR1) polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) on adult height, breast development, uterine volume and bone mineral density (BMD). We studied 91 TS patients from a tertiary hospital using adult estrogen dose. In our group, ESR1 rs2234693 was associated with femoral neck and total hip BMD, and it accounted for around 10% of BMD variability in both sites (P < 0.01). Patients homozygous for C allele in this polymorphism had significantly lower femoral neck BMD (0.699 ± 0.065 g/cm2 vs 0.822 ± 0.113 g/cm2, P = 0.008) and total hip BMD (0.777 ± 0.118 g/cm2 vs 0.903 ± 0.098 g/cm2, P = 0.009) than patients homozygous for T allele. The other four ESR1 polymorphisms were not able to predict any of the above estrogen therapy outcomes in an isolated manner. Patients homozygous for the haplotype GCG formed by polymorphisms rs543650, rs2234693 and rs9340799 had an even more significantly lower femoral neck BMD (0.666 ± 0.049 vs 0.820 ± 0.105 g/cm2, P = 0.0047) and total hip BMD (0.752 ± 0.093 vs 0.908 ± 0.097 g/cm2, P = 0.0029) than patients homozygous for haplotypes with a T allele in rs2234693. In conclusion, homozygosity for C allele in ESR1 rs2234693 and/or for GCG haplotype appears to be associated with lower femoral neck and total hip BMD. We believe that the identification of polymorphisms related to estrogen outcomes may contribute to individualization of treatment in TS.
大多数特纳综合征（TS）患者因高促性腺激素性性腺功能减退需要激素替代疗法；然而，个体治疗结果差异很大。我们的目的是评估五个雌激素受体1基因（ESR1）多态性（rs543650、rs1038304、rs2046210、rs2234693和rs9340799）对成年身高、乳房发育、子宫体积和骨密度（BMD）的影响。我们使用成人雌激素剂量对一家三级医院的91例TS患者进行了研究。在我们的研究组中，ESR1 rs2234693与股骨颈和全髋部骨密度相关，且在两个部位的骨密度变异性中占比约10%（P < 0.01）。该多态性中C等位基因纯合的患者股骨颈骨密度（0.699±0.065 g/cm² 对比 0.822±0.113 g/cm²，P = 0.008）和全髋部骨密度（0.777±0.118 g/cm² 对比 0.903±0.098 g/cm²，P = 0.009）显著低于T等位基因纯合的患者。其他四个ESR1多态性无法单独预测上述任何雌激素治疗结果。由多态性rs543650、rs2234693和rs9340799组成的单倍型GCG纯合的患者，其股骨颈骨密度（0.666±0.049对比0.820±0.105 g/cm²，P = 0.0047）和全髋部骨密度（0.752±0.093对比0.908±0.097 g/cm²，P = 0.0029）比rs2234693中T等位基因单倍型纯合的患者更低。总之，ESR1 rs2234693中C等位基因纯合和/或GCG单倍型纯合似乎与较低的股骨颈和全髋部骨密度相关。我们认为，识别与雌激素治疗结果相关的多态性可能有助于TS治疗的个体化。
