Effects of polymorphisms of the CYP450 enzyme genes on estrogen status and the risk for osteoporosis

Nicola Napoli, Reina Armamento-Villareal

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Several enzymes belonging to the CYP450 group are involved in the biosynthesis and metabolism of estrogen. Polymorphisms of the genes encoding for these enzymes have been linked to hormone-related diseases, notably breast cancer. These associations are based on the notion that certain variants of these enzymes have altered activity resulting in an alteration in estrogenic state, which in turn leads to differences in the risk for hormone-related disorders. Recent studies have indicated that these same polymorphisms are also important determinants of bone mineral density (BMD) and osteoporosis, another hormone-dependent condition. To name some, certain polymorphisms in the CYP19, CYP17, CYP1A1 and CYP1B1 genes have been found to affect BMD. So far, in this context, the most extensively investigated polymorphisms are those of the CYP19, the gene that codes for aromatase, an important enzyme in the estrogen biosynthetic pathway that converts androgenic steroids to estrogen. To our knowledge, four important polymorphisms of the aromatase gene are associated with differences in BMD and the risk for osteoporosis. Newer data further suggest that response to estrogen or hormone therapy may also be influenced by polymorphisms in the aromatase gene. And finally, a recent report indicates that polymorphisms of the genes encoding for the enzymes that metabolize estrogen are also important determinants of BMD. The C4887A polymorphism in the CYP1A1 gene is found to be associated with increased estrogen catabolism and lower femoral BMD in women carrying the A allele, present in 19% of the population. A similar (unpublished) observation is also noted for one of the CYP1B1 gene polymorphisms. The main focus of this review is to examine the effects of polymorphisms of the CYP 450 enzyme genes involved in estrogen biosynthesis and metabolism on BMD and the risk for osteoporosis.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalCurrent Pharmacogenomics
Volume5
Issue number1
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Osteoporosis
Estrogens
Aromatase
Bone Density
Enzymes
Genes
Hormones
Cytochrome P-450 CYP1A1
Steroid 17-alpha-Hydroxylase
Biosynthetic Pathways
Thigh
Names
Alleles
Steroids
Observation
Breast Neoplasms
Population

Keywords

  • Bone mineral density
  • CYP450 enzymes
  • Estrogen
  • Osteoporosis

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

Cite this

Effects of polymorphisms of the CYP450 enzyme genes on estrogen status and the risk for osteoporosis. / Napoli, Nicola; Armamento-Villareal, Reina.

In: Current Pharmacogenomics, Vol. 5, No. 1, 03.2007, p. 1-10.

Research output: Contribution to journalArticle

Napoli, Nicola ; Armamento-Villareal, Reina. / Effects of polymorphisms of the CYP450 enzyme genes on estrogen status and the risk for osteoporosis. In: Current Pharmacogenomics. 2007 ; Vol. 5, No. 1. pp. 1-10.
@article{eea4a1d580e749fe87712491a0006301,
title = "Effects of polymorphisms of the CYP450 enzyme genes on estrogen status and the risk for osteoporosis",
abstract = "Several enzymes belonging to the CYP450 group are involved in the biosynthesis and metabolism of estrogen. Polymorphisms of the genes encoding for these enzymes have been linked to hormone-related diseases, notably breast cancer. These associations are based on the notion that certain variants of these enzymes have altered activity resulting in an alteration in estrogenic state, which in turn leads to differences in the risk for hormone-related disorders. Recent studies have indicated that these same polymorphisms are also important determinants of bone mineral density (BMD) and osteoporosis, another hormone-dependent condition. To name some, certain polymorphisms in the CYP19, CYP17, CYP1A1 and CYP1B1 genes have been found to affect BMD. So far, in this context, the most extensively investigated polymorphisms are those of the CYP19, the gene that codes for aromatase, an important enzyme in the estrogen biosynthetic pathway that converts androgenic steroids to estrogen. To our knowledge, four important polymorphisms of the aromatase gene are associated with differences in BMD and the risk for osteoporosis. Newer data further suggest that response to estrogen or hormone therapy may also be influenced by polymorphisms in the aromatase gene. And finally, a recent report indicates that polymorphisms of the genes encoding for the enzymes that metabolize estrogen are also important determinants of BMD. The C4887A polymorphism in the CYP1A1 gene is found to be associated with increased estrogen catabolism and lower femoral BMD in women carrying the A allele, present in 19{\%} of the population. A similar (unpublished) observation is also noted for one of the CYP1B1 gene polymorphisms. The main focus of this review is to examine the effects of polymorphisms of the CYP 450 enzyme genes involved in estrogen biosynthesis and metabolism on BMD and the risk for osteoporosis.",
keywords = "Bone mineral density, CYP450 enzymes, Estrogen, Osteoporosis",
author = "Nicola Napoli and Reina Armamento-Villareal",
year = "2007",
month = "3",
doi = "10.2174/157016007780077194",
language = "English",
volume = "5",
pages = "1--10",
journal = "Current Pharmacogenomics",
issn = "1570-1603",
publisher = "Bentham Science Publishers B.V.",
number = "1",

}

TY - JOUR

T1 - Effects of polymorphisms of the CYP450 enzyme genes on estrogen status and the risk for osteoporosis

AU - Napoli, Nicola

AU - Armamento-Villareal, Reina

PY - 2007/3

Y1 - 2007/3

N2 - Several enzymes belonging to the CYP450 group are involved in the biosynthesis and metabolism of estrogen. Polymorphisms of the genes encoding for these enzymes have been linked to hormone-related diseases, notably breast cancer. These associations are based on the notion that certain variants of these enzymes have altered activity resulting in an alteration in estrogenic state, which in turn leads to differences in the risk for hormone-related disorders. Recent studies have indicated that these same polymorphisms are also important determinants of bone mineral density (BMD) and osteoporosis, another hormone-dependent condition. To name some, certain polymorphisms in the CYP19, CYP17, CYP1A1 and CYP1B1 genes have been found to affect BMD. So far, in this context, the most extensively investigated polymorphisms are those of the CYP19, the gene that codes for aromatase, an important enzyme in the estrogen biosynthetic pathway that converts androgenic steroids to estrogen. To our knowledge, four important polymorphisms of the aromatase gene are associated with differences in BMD and the risk for osteoporosis. Newer data further suggest that response to estrogen or hormone therapy may also be influenced by polymorphisms in the aromatase gene. And finally, a recent report indicates that polymorphisms of the genes encoding for the enzymes that metabolize estrogen are also important determinants of BMD. The C4887A polymorphism in the CYP1A1 gene is found to be associated with increased estrogen catabolism and lower femoral BMD in women carrying the A allele, present in 19% of the population. A similar (unpublished) observation is also noted for one of the CYP1B1 gene polymorphisms. The main focus of this review is to examine the effects of polymorphisms of the CYP 450 enzyme genes involved in estrogen biosynthesis and metabolism on BMD and the risk for osteoporosis.

AB - Several enzymes belonging to the CYP450 group are involved in the biosynthesis and metabolism of estrogen. Polymorphisms of the genes encoding for these enzymes have been linked to hormone-related diseases, notably breast cancer. These associations are based on the notion that certain variants of these enzymes have altered activity resulting in an alteration in estrogenic state, which in turn leads to differences in the risk for hormone-related disorders. Recent studies have indicated that these same polymorphisms are also important determinants of bone mineral density (BMD) and osteoporosis, another hormone-dependent condition. To name some, certain polymorphisms in the CYP19, CYP17, CYP1A1 and CYP1B1 genes have been found to affect BMD. So far, in this context, the most extensively investigated polymorphisms are those of the CYP19, the gene that codes for aromatase, an important enzyme in the estrogen biosynthetic pathway that converts androgenic steroids to estrogen. To our knowledge, four important polymorphisms of the aromatase gene are associated with differences in BMD and the risk for osteoporosis. Newer data further suggest that response to estrogen or hormone therapy may also be influenced by polymorphisms in the aromatase gene. And finally, a recent report indicates that polymorphisms of the genes encoding for the enzymes that metabolize estrogen are also important determinants of BMD. The C4887A polymorphism in the CYP1A1 gene is found to be associated with increased estrogen catabolism and lower femoral BMD in women carrying the A allele, present in 19% of the population. A similar (unpublished) observation is also noted for one of the CYP1B1 gene polymorphisms. The main focus of this review is to examine the effects of polymorphisms of the CYP 450 enzyme genes involved in estrogen biosynthesis and metabolism on BMD and the risk for osteoporosis.

KW - Bone mineral density

KW - CYP450 enzymes

KW - Estrogen

KW - Osteoporosis

UR - http://www.scopus.com/inward/record.url?scp=33947114246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947114246&partnerID=8YFLogxK

U2 - 10.2174/157016007780077194

DO - 10.2174/157016007780077194

M3 - Article

AN - SCOPUS:33947114246

VL - 5

SP - 1

EP - 10

JO - Current Pharmacogenomics

JF - Current Pharmacogenomics

SN - 1570-1603

IS - 1

ER -