Sasaki Masahiro, Tanaka Yuichiro, Sakuragi Noriaki, Dahiya Rajvir
Department of Urology, Urology Research Center, University of California, San Francisco, CA 94121, USA.
Eur J Clin Pharmacol. 2003 Sep;59(5-6):389-93. doi: 10.1007/s00228-003-0609-z. Epub 2003 Aug 16.
Estrogen receptor 1 ( ESR1) plays an important role in various estrogen-related diseases, the incidences of which are significantly lower in the Japanese population than in Western populations. We hypothesize that polymorphisms in exon 1 of the ESR1 gene are associated with a lower incidence of estrogen-related diseases in the Japanese population.
The genetic distributions of six different ESR1 gene polymorphisms were investigated among 200 Japanese, 200 Americans and 112 Germans using a novel sequence-specific polymerase chain reaction (SSP) technique and direct DNA sequencing.
The frequencies of variant genotypes on codons 10 and 87 located on exon 1 were significantly lower in the Japanese population than other populations. The polymorphism on codon 87 was not detected in the Japanese population, although other populations showed the homozygous and heterozygous variant genotype on this codon. Other loci, intron 1, and codons 243 and 594 were not different among these populations.
This is the first report to demonstrate the polymorphisms at codons 10 and 87 of ESR1 are significantly low for the Japanese population. Thus, inherited alterations in ESR1 polymorphisms may be associated with changes of estrogen effects and, thereby, may possibly explain inter-population differences in incidences of estrogen-mediated diseases.
雌激素受体1（ESR1）在各种雌激素相关疾病中起重要作用，这些疾病在日本人群中的发病率明显低于西方人群。我们假设ESR1基因外显子1中的多态性与日本人群中雌激素相关疾病的较低发病率有关。
使用一种新型的序列特异性聚合酶链反应（SSP）技术和直接DNA测序，在200名日本人、200名美国人和112名德国人中研究了六种不同的ESR1基因多态性的基因分布。
位于外显子1上密码子10和87处的变异基因型频率在日本人群中明显低于其他人群。在日本人群中未检测到密码子87处的多态性，而其他人群在该密码子上显示出纯合和杂合变异基因型。其他位点，即内含子1以及密码子243和594在这些人群中没有差异。
这是第一份证明ESR1基因密码子10和87处的多态性在日本人群中显著较低的报告。因此，ESR1多态性的遗传改变可能与雌激素效应的变化有关，从而可能解释雌激素介导疾病发病率的人群间差异。
