Relationship between single nucleotide polymorphisms in CYP1A1 and CYP1B1 genes and the bone mineral density and serum lipid profiles in postmenopausal Japanese women taking hormone therapy.
OBJECTIVE
The genetic variations of the genes encoding cytochrome P-450 enzymes are considered to play an important role in the metabolism of estradiol. The objective of this study was to evaluate the relationships among single nucleotide polymorphisms (SNPs) of cytochrome P-450 genes, lumbar bone mineral density (BMD), and serum lipids and to determine the effects of hormone therapy (HT).


METHODS
The participants were 124 Japanese women who had been diagnosed with osteopenia or osteoporosis and were taking HT for 12 months. Seven single nucleotide polymorphisms in the CYP1A1 and CYP1B1 genes were characterized. Lumbar BMD and the levels of serum lipids were measured before and after HT.


RESULTS
A single nucleotide polymorphism in exon 3 of CYP1B1 was found to be significantly associated with the effect of HT on BMD and low-density lipoprotein cholesterol both in univariate and multivariate analyses. In the women with the GG genotype of L432V, the responses to HT of BMD and low-density lipoprotein cholesterol markedly decreased. The serum follicle-stimulating hormone level after HT was significantly higher in the women with the GG genotype of L432V.


CONCLUSIONS
These results suggest that the L432V polymorphism in the CYP1B1 gene could therefore be used to predict the effect of HT on lumbar BMD and low-density lipoprotein cholesterol in Japanese women.
Quan
Jinhua
J
Division of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital, Asahimachi-dori, Niigata, Japan.
Yahata
Tetsuro
T
Tamura
Nozomi
N
Nagata
Hiroshi
H
Tanaka
Kenichi
K
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D006801:Humans; D007564:Japan; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause
D008078:Cholesterol, LDL; D008055:Lipids; D005640:Follicle Stimulating Hormone; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1