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Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density.
J Bone Miner Res. 2005 Feb; 20(2):232-9.JB

Abstract

In this study, we evaluated the effect of polymorphisms of the CYP1A1 gene, linked to hormone-related 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 = 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 = 0.03), suggestive of an accelerated estrogen catabolism in these (CA + AA) individuals. They also had significantly lower BMD (g/cm2) in all regions of the femur than subjects with the CC genotype, (total hip: 0.809 +/- 0.02 versus 0.865 +/- 0.01; neck: 0.671 +/- 0.02 versus 0.722 +/- 0.01; trochanter: 0.614 +/- 0.02 versus 0.656 +/- 0.01; and intertrochanter: 0.969 +/- 0.03 versus 1.039 +/- 0.01; all p < 0.05). No significant effect of this gene polymorphism was detected on lumbar spine BMD. Urinary NTx, a marker for bone resorption, was also significantly higher in the CA + AA compared with the CC variants (186.09 +/- 16.15 versus 124.00 +/- 11.87 nmol of bone collagen equivalent/mmol of creatinine; p = 0.003). Genotype frequencies for this polymorphism showed CC as the most common genotype (127/156), followed by CA (28/156), whereas AA was rare (1/156).

CONCLUSION

Women with the A allele seem to have increased estrogen catabolism, as indicated by higher urinary estrogen metabolites and lower free estradiol index. This is associated with increased bone resorption and lower femoral BMD in those with the A allele. Our data, therefore, suggest that, through its effect on the rate of estrogen catabolism, the C4887A polymorphism of the CYP1A1 gene may represent a possible genetic risk factor for osteoporosis.

Authors+Show Affiliations

Division of Bone and Mineral Diseases, Washington University School of Medicine, St Louis, MO 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15647817

Citation

Napoli, Nicola, et al. "Effect of CYP1A1 Gene Polymorphisms On Estrogen Metabolism and Bone Density." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 20, no. 2, 2005, pp. 232-9.
Napoli N, Villareal DT, Mumm S, et al. Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density. J Bone Miner Res. 2005;20(2):232-9.
Napoli, N., Villareal, D. T., Mumm, S., Halstead, L., Sheikh, S., Cagaanan, M., Rini, G. B., & Armamento-Villareal, R. (2005). Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 20(2), 232-9.
Napoli N, et al. Effect of CYP1A1 Gene Polymorphisms On Estrogen Metabolism and Bone Density. J Bone Miner Res. 2005;20(2):232-9. PubMed PMID: 15647817.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density. AU - Napoli,Nicola, AU - Villareal,Dennis T, AU - Mumm,Steven, AU - Halstead,Linda, AU - Sheikh,Sharmin, AU - Cagaanan,Manuel, AU - Rini,Giovam Battista, AU - Armamento-Villareal,Reina, Y1 - 2004/11/16/ PY - 2004/05/21/received PY - 2004/09/02/revised PY - 2004/09/14/accepted PY - 2005/1/14/pubmed PY - 2005/6/9/medline PY - 2005/1/14/entrez SP - 232 EP - 9 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 20 IS - 2 N2 - UNLABELLED: In this study, we evaluated the effect of polymorphisms of the CYP1A1 gene, linked to hormone-related 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 = 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 = 0.03), suggestive of an accelerated estrogen catabolism in these (CA + AA) individuals. They also had significantly lower BMD (g/cm2) in all regions of the femur than subjects with the CC genotype, (total hip: 0.809 +/- 0.02 versus 0.865 +/- 0.01; neck: 0.671 +/- 0.02 versus 0.722 +/- 0.01; trochanter: 0.614 +/- 0.02 versus 0.656 +/- 0.01; and intertrochanter: 0.969 +/- 0.03 versus 1.039 +/- 0.01; all p < 0.05). No significant effect of this gene polymorphism was detected on lumbar spine BMD. Urinary NTx, a marker for bone resorption, was also significantly higher in the CA + AA compared with the CC variants (186.09 +/- 16.15 versus 124.00 +/- 11.87 nmol of bone collagen equivalent/mmol of creatinine; p = 0.003). Genotype frequencies for this polymorphism showed CC as the most common genotype (127/156), followed by CA (28/156), whereas AA was rare (1/156). CONCLUSION: Women with the A allele seem to have increased estrogen catabolism, as indicated by higher urinary estrogen metabolites and lower free estradiol index. This is associated with increased bone resorption and lower femoral BMD in those with the A allele. Our data, therefore, suggest that, through its effect on the rate of estrogen catabolism, the C4887A polymorphism of the CYP1A1 gene may represent a possible genetic risk factor for osteoporosis. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/15647817/Effect_of_CYP1A1_gene_polymorphisms_on_estrogen_metabolism_and_bone_density_ L2 - https://doi.org/10.1359/JBMR.041110 DB - PRIME DP - Unbound Medicine ER -