雌激素受体-β基因胞嘧啶-腺嘌呤重复多态性与绝经症状的关联。

Association of cytosine-adenine repeat polymorphism of the estrogen receptor-beta gene with menopausal symptoms.

作者信息

Takeo Chikari, Negishi Etsuko, Nakajima Aya, Ueno Koichi, Tatsuno Ichiro, Saito Yasushi, Amano Keiko, Hirai Aizan

机构信息

Department of General Medicine, Chiba Pre fectural Togane Hospital, Chiba, Japan.

出版信息

Gend Med. 2005 Jun;2(2):96-105. doi: 10.1016/s1550-8579(05)80016-6.

DOI:10.1016/s1550-8579(05)80016-6

PMID:16115604

Abstract

BACKGROUND

The nature and severity of menopausal symptoms are highly variable among women. Polymorphisms of the estrogen receptor-beta (ERbeta) gene, such as cytosine-adenine (CA) dinucleotide repeats in intron 5, have been implicated in various diseases.

OBJECTIVE

We investigated the possible role of a CA dinucleotide repeat polymorphism in intron 5 of the ERbeta gene in the occurrence of menopausal and premenstrual symptoms.

METHODS

Fifty-one postmenopausal Japanese women were interviewed about premenstrual symptoms, menopausal symptoms, and use of hormone replacement therapy. Menopausal symptoms were divided into vasomotor, psychological, and musculoskeletal symptoms, and summary scores were created on the basis of severity. CA repeat polymorphism of the ERbeta gene was examined using denaturing high-performance liquid chromatography with the WAVE DNA Fragment Analysis System (Transgenomic Inc., Omaha, Nebraska).

RESULTS

The number of CA repeats of the ERP gene ranged from 14 to 25, and subjects could be divided into 3 groups: those with < or =17 repeats, or extremely short (E); 18 to 21 repeats, or short (S); and > or =22 repeats, or long (L). Four genotypes of CA repeats (EL, SS, SL, and LL) were found among the subjects, with SL being the most common. Relative to subjects with the SL genotype, women with SS had a 7.0-fold increased risk of vasomotor symptoms (odds ratio [OR] = 7.0; 95% CI, 1.25-39.15; P < 0.05), a 13.0-fold higher risk of psychological symptoms (OR = 13.0; 95% CI, 1.44-117.2; P < 0.01), and a 7.6-fold increased risk of premenstrual symptoms (OR = 7.6; 95% CI, 1.61-35.9; P = 0.01). The EL genotype was associated with an increased risk of vasomotor symptoms (P < 0.05), depression (P < 0.01), and premenstrual symptoms (P < 0.01).

CONCLUSIONS

CA repeat polymorphism of the ERbeta gene may be associated with menopausal and premenstrual symptoms. Premenstrual symptom scores were significantly related to menopausal symptom scores.

摘要

背景

绝经症状的性质和严重程度在女性中差异很大。雌激素受体β（ERβ）基因的多态性，如内含子5中的胞嘧啶-腺嘌呤（CA）二核苷酸重复序列，与多种疾病有关。

目的

我们研究了ERβ基因内含子5中CA二核苷酸重复多态性在绝经症状和经前症状发生中的可能作用。

方法

对51名绝经后日本女性进行了关于经前症状、绝经症状和激素替代疗法使用情况的访谈。绝经症状分为血管舒缩症状、心理症状和肌肉骨骼症状，并根据严重程度创建汇总分数。使用变性高效液相色谱法和WAVE DNA片段分析系统（Transgenomic公司，内布拉斯加州奥马哈）检测ERβ基因的CA重复多态性。

结果

ERP基因的CA重复次数范围为14至25，受试者可分为3组：重复次数≤17次，即极短（E）组；18至21次，即短（S）组；≥22次，即长（L）组。在受试者中发现了4种CA重复基因型（EL、SS、SL和LL），其中SL最为常见。与SL基因型的受试者相比，SS基因型的女性出现血管舒缩症状的风险增加7.0倍（优势比[OR]=7.0；95%可信区间，1.25-39.15；P<0.05），心理症状的风险高13.0倍（OR=13.0；95%可信区间，1.44-117.2；P<0.01），经前症状的风险增加7.6倍（OR=7.6；95%可信区间，1.61-35.9；P=0.01）。EL基因型与血管舒缩症状风险增加（P<0.05）、抑郁（P<0.01）和经前症状风险增加（P<0.01）有关。