Advanced

The Impact of Estradiol on Bone Mineral Density is modulated by The Specific Estrogen Receptor-{alpha} Cofactor RIZ1 Insertion/Deletion Polymorphism.

Grundberg, Elin; Åkesson, Kristina LU ; Kindmark, Andreas; Gerdhem, Paul LU ; Holmberg, Anna H LU ; Mellstrom, Dan; Ljunggren, Osten; Orwoll, Eric; Mallmin, Hans and Ohlsson, Claes, et al. (2007) In Journal of Clinical Endocrinology and Metabolism 92(Mar 13). p.2300-2306
Abstract
Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ER -cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ER alpha function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/ deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmo OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in... (More)
Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ER -cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ER alpha function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/ deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmo OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmo University Hospital, and Uppsala University Hospital. Participants: In total, 4058 men and women, aged 69 -81 yr, were randomly selected from population registries. Main Outcome Measures: BMD(grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. Results: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(+/+) group (r = 0.19 vs. r = 0.08, P < 0.05). Conclusions: These large-scale studies of elderly men and women indicate that the ER alpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
92
issue
Mar 13
pages
2300 - 2306
publisher
The Endocrine Society
external identifiers
  • wos:000247061700050
  • scopus:34347254665
ISSN
1945-7197
DOI
10.1210/jc.2006-1572
language
English
LU publication?
yes
id
16b4dae4-f21a-4a17-a348-e4e38c55f541 (old id 166608)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17356055&dopt=Abstract
date added to LUP
2007-07-23 09:56:57
date last changed
2017-01-01 07:02:11
@article{16b4dae4-f21a-4a17-a348-e4e38c55f541,
  abstract     = {Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ER -cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ER alpha function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/ deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmo OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmo University Hospital, and Uppsala University Hospital. Participants: In total, 4058 men and women, aged 69 -81 yr, were randomly selected from population registries. Main Outcome Measures: BMD(grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. Results: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P &lt; 0.001; trochanter, P &lt; 0.01; lumbar spine, P &lt; 0.05; total body, P &lt; 0.01) and men (lumbar spine, P &lt; 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(+/+) group (r = 0.19 vs. r = 0.08, P &lt; 0.05). Conclusions: These large-scale studies of elderly men and women indicate that the ER alpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.},
  author       = {Grundberg, Elin and Åkesson, Kristina and Kindmark, Andreas and Gerdhem, Paul and Holmberg, Anna H and Mellstrom, Dan and Ljunggren, Osten and Orwoll, Eric and Mallmin, Hans and Ohlsson, Claes and Brandstrom, Helena},
  issn         = {1945-7197},
  language     = {eng},
  number       = {Mar 13},
  pages        = {2300--2306},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {The Impact of Estradiol on Bone Mineral Density is modulated by The Specific Estrogen Receptor-{alpha} Cofactor RIZ1 Insertion/Deletion Polymorphism.},
  url          = {http://dx.doi.org/10.1210/jc.2006-1572},
  volume       = {92},
  year         = {2007},
}