Polymorphisms in the estrogen receptor β (ESR2) gene are associated with bone mineral density in Caucasian men and women

Shoji Ichikawa, Daniel L. Koller, Munro Peacock, Michelle L. Johnson, Dongbing Lai, Siu Hui, C. Conrad Johnston, Tatiana Foroud, Michael Econs

Research output: Contribution to journalArticle

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Abstract

Context: A major determinant of osteoporotic fractures is peak bone mineral density (BMD), which is a highly heritable trait. Recently, we identified significant linkage for hip BMD in premenopausal sister pairs at chromosome 14q (LOD score = 3.5), where the estrogen receptor β gene (ESR2) is located. Objective: The objective of the study was to determine whether ESR2 polymorphisms are associated with normal BMD variation. Design: This was a population-based genetic association study, using 11 single nucleotide polymorphisms (SNPs) distributed across the ESR2 gene. Setting: The study was conducted at an academic research laboratory and medical center. Patients and Other Participants: A total of 411 healthy men (aged 18-61 yr) and 1291 healthy premenopausal women (aged 20-50 yr) living in Indiana participated in the study. Intervention(s): There were no interventions. Main Outcome Measure(s): The main outcome measures were SNP genotype distributions and their association with BMD at the femoral neck and lumbar spine. Results: Significant association of spine BMD was found with three SNPs in men and one SNP in women (P ≤ 0.05). The conditional linkage analysis using the ESR2 haplotypes showed that the ESR2 gene accounts for, at most, 18% of the original linkage. Conclusions: ESR2 polymorphisms are significantly associated with bone mass in both men and women. However, the ESR2 gene is not entirely responsible for our original linkage, and an additional gene(s) in chromosome 14q contributes to the determination of BMD.

Original languageEnglish
Pages (from-to)5921-5927
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number11
DOIs
StatePublished - Nov 2005

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Polymorphism
Estrogen Receptors
Bone Density
Minerals
Bone
Genes
Single Nucleotide Polymorphism
Nucleotides
Chromosomes
Spine
Outcome Assessment (Health Care)
Pelvic Bones
Osteoporotic Fractures
Femur Neck
Population Genetics
Genetic Association Studies
Haplotypes
Research laboratories
Biomedical Research
Siblings

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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Polymorphisms in the estrogen receptor β (ESR2) gene are associated with bone mineral density in Caucasian men and women. / Ichikawa, Shoji; Koller, Daniel L.; Peacock, Munro; Johnson, Michelle L.; Lai, Dongbing; Hui, Siu; Johnston, C. Conrad; Foroud, Tatiana; Econs, Michael.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 11, 11.2005, p. 5921-5927.

Research output: Contribution to journalArticle

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abstract = "Context: A major determinant of osteoporotic fractures is peak bone mineral density (BMD), which is a highly heritable trait. Recently, we identified significant linkage for hip BMD in premenopausal sister pairs at chromosome 14q (LOD score = 3.5), where the estrogen receptor β gene (ESR2) is located. Objective: The objective of the study was to determine whether ESR2 polymorphisms are associated with normal BMD variation. Design: This was a population-based genetic association study, using 11 single nucleotide polymorphisms (SNPs) distributed across the ESR2 gene. Setting: The study was conducted at an academic research laboratory and medical center. Patients and Other Participants: A total of 411 healthy men (aged 18-61 yr) and 1291 healthy premenopausal women (aged 20-50 yr) living in Indiana participated in the study. Intervention(s): There were no interventions. Main Outcome Measure(s): The main outcome measures were SNP genotype distributions and their association with BMD at the femoral neck and lumbar spine. Results: Significant association of spine BMD was found with three SNPs in men and one SNP in women (P ≤ 0.05). The conditional linkage analysis using the ESR2 haplotypes showed that the ESR2 gene accounts for, at most, 18{\%} of the original linkage. Conclusions: ESR2 polymorphisms are significantly associated with bone mass in both men and women. However, the ESR2 gene is not entirely responsible for our original linkage, and an additional gene(s) in chromosome 14q contributes to the determination of BMD.",
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