Association of cytosine-adenine repeat polymorphism of the estrogen receptor-beta gene with menopausal symptoms.
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.
Takeo
Chikari
C
Department of General Medicine, Chiba Pre fectural Togane Hospital, Chiba, Japan. chikari@prefhosp.togane.chiba.jp
Negishi
Etsuko
E
Nakajima
Aya
A
Ueno
Koichi
K
Tatsuno
Ichiro
I
Saito
Yasushi
Y
Amano
Keiko
K
Hirai
Aizan
A
D000225:Adenine / Q000378:metabolism; D003596:Cytosine / Q000378:metabolism; D003863:Depression / Q000453:epidemiology / Q000235:genetics; D018900:Dinucleotide Repeats; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D006261:Headache / Q000453:epidemiology / Q000235:genetics; D019584:Hot Flashes / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011293:Premenstrual Syndrome / Q000453:epidemiology* / Q000235:genetics*; D012044:Regression Analysis
D047629:Estrogen Receptor beta; D003596:Cytosine; D000225:Adenine