The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-α cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism

Elin Grundberg, Kristina Åkesson, Andreas Kindmark, Paul Gerdhem, Anna Holmberg, Dan Mellström, Östen Ljunggren, Eric Orwoll, Hans Mallmin, Claes Ohlsson, Helena Brändström

Research output: Contribution to journalArticle

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Abstract

Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-α as well as ER-β. The specific ERα cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERα 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 crosssectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö 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 ERα 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.

Original languageEnglish (US)
Pages (from-to)2300-2306
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Retinoblastoma
Zinc Fingers
Polymorphism
Estrogen Receptors
Bone Density
Minerals
Zinc
Estradiol
Bone
Proteins
Spine
Femur Neck
Genotype
Femur
Estrogens
Population
Registries
Outcome Assessment (Health Care)
Prospective Studies
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-α cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism. / Grundberg, Elin; Åkesson, Kristina; Kindmark, Andreas; Gerdhem, Paul; Holmberg, Anna; Mellström, Dan; Ljunggren, Östen; Orwoll, Eric; Mallmin, Hans; Ohlsson, Claes; Brändström, Helena.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 6, 06.2007, p. 2300-2306.

Research output: Contribution to journalArticle

Grundberg, Elin ; Åkesson, Kristina ; Kindmark, Andreas ; Gerdhem, Paul ; Holmberg, Anna ; Mellström, Dan ; Ljunggren, Östen ; Orwoll, Eric ; Mallmin, Hans ; Ohlsson, Claes ; Brändström, Helena. / The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-α cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 6. pp. 2300-2306.
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abstract = "Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-α as well as ER-β. The specific ERα cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERα 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 crosssectional study, the Swedish MrOS Study, and the Malm{\"o} OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malm{\"o} 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 ERα 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.",
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T1 - The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-α cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism

AU - Grundberg, Elin

AU - Åkesson, Kristina

AU - Kindmark, Andreas

AU - Gerdhem, Paul

AU - Holmberg, Anna

AU - Mellström, Dan

AU - Ljunggren, Östen

AU - Orwoll, Eric

AU - Mallmin, Hans

AU - Ohlsson, Claes

AU - Brändström, Helena

PY - 2007/6

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N2 - Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-α as well as ER-β. The specific ERα cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERα 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 crosssectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö 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 ERα 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.

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