Pharmacogenetics of hormone replacement therapy for climacteric symptoms.
Hormone replacement therapy (HRT) is highly effective for women suffering from climacteric symptoms, with occasionally severe side effects. To determine which women needs HRT for climacteric symptoms indeed, pharmacogenetical approach for HRT was performed. Under the condition of minimal HRT, 33 patients required HRT for more than 1 year and the remaining 156 did not. Three single nucleotide polymorphisms (SNPs) in estrogen receptor alpha (ERalpha) gene and 3 SNPs and a microsatellite polymorphism in estrogen receptor beta (ERbeta) gene were analyzed using LightTyper and PCR. Homozygous for 18 CA repeats of D14S1026 (OR 8.00, 95% CI 2.56-25.02, P<0.001) and rs1256049 (OR 6.35, 95% CI 2.38-16.92, P=0.004) in ERbeta associated with minimal HRT. In contrast, rs1271572 in 789bp upstream region of ERbeta (OR 0.30, 95% CI 0.14-0.65, P=0.002) gene decreased HRT. rs2228480 in ERalpha gene also increased HRT. Tailored decisions can be expected on the future use of HRT referring genetic polymorphisms of individuals.
Takeo
Chikari
C
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Ugai
Kanako
K
Araki
Jungo
J
Zhang
Ling
L
Baba
Masanori
M
Ohashi
Wataru
W
Ueno
Koichi
K
Suzuki
Yoichi
Y
Amano
Keiko
K
Hirai
Aizan
A
Muramatsu
Masaaki
M
D004958:Estradiol / Q000008:administration & dosage*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000235:genetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D006720:Homozygote; D006801:Humans; D007564:Japan; D008593:Menopause / Q000187:drug effects / Q000235:genetics*; D018895:Microsatellite Repeats; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol