Effect of CYP1A1 Gene Polymorphisms on Estrogen Metabolism and Bone Density

Abstract

In this study, we evaluated the effect of polymorphisms of the CYP1A1 gene, linked to hormonerelated cancers, on estrogen metabolism and BMD. We found that variants carrying the A allele (CA and AA) for the C4887A polymorphism have a significantly higher degree of estrogen catabolism and lower femoral BMD.Introduction: Polymorphisms of the CYP1A1 gene, one of the key enzymes that metabolize estrogen, have been linked with hormone-related cancers. We investigated the impact of these polymorphisms on estrogen metabolism and BMD, which is another hormone-dependent health issue. Materials and Methods: One hundred seventy postmenopausal women (mean age, 63.5 ± 0.6 years) participated in the study, but analysis was limited to 156 white women. Genotyping was performed by restriction fragment length polymorphism analysis, urinary estrogen metabolites by enzyme immunoassay, serum estradiol by ultrasensitive radioimmunoassay, serum sex hormone-binding globulin by immunoradiometric assay, and BMD by DXA. Differences in the levels of urinary metabolites and BMD among the different variants were analyzed by analysis of covariance, whereas differences in free estradiol index, urinary N-telopeptide of type 1 collagen (NTx), and bone size were compared by one-way ANOVA. Results: We found that subjects carrying the A allele (CA or AA) for the C4887A polymorphism of the CYP1A1 gene have significantly lower free estradiol index (0.323 ± 0.08 versus 0.506 ± 0.04; p ‫ס‬ 0.04; pmol/nmol) and higher levels of total urinary estrogen metabolites (ng/mg Cr) than CC subjects (27.92 ± 2.03 versus 21.15 ± 1.04; p ‫ס‬ 0.03), suggestive of an accelerated estrogen catabolism in these (CA + AA) individuals. They also had significantly lower BMD (g/cm

The association of common polymorphisms in the QPCT gene with bone mineral density in the Chinese population

“…The CYP450 enzymes metabolize estrogen. The C allele of the CYP1B1 G1294C polymorphism is associated with increased estrogen catabolism and lower BMD (Napoli et al 2004). POMC, a precursor for adrenocorticotropic hormone, acts on the cortex of the adrenal glands, leading to the production of glucocorticoid.…”

High aromatase activity in hypogonadal men is associated with higher spine bone mineral density, increased truncal fat and reduced lean mass

“…The CV for these assays in our laboratory are !10%. The free E 2 index (FEI) was calculated as the molar ratio of total E 2 to SHBG (pmol/nmol) (19). The free androgen index (FAI) and the E 2 to testosterone ratio (E 2 :T) were calculated by using the formula previously described by Sowers et al (20): FAI: 100!T (ng/dl)/28.84!SHBG (nM); E 2 :TZ10!E 2 / testosterone, both of which are unit free.…”

CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

“…The substrates of CYP1B1 enzymatic activity are also the inducers of gene transcription, consistent with CYP1A1 activity [12]. The polymorphisms of CYP1A1 and CYP1B1 gene had been studied in relation to the hormonally relevant diseases, such as endometriosis, breast cancer, endometrial adenocarcinoma [13][14][15][16][17].…”