Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone mineral density in white men or women

S. Ichikawa, M. L. Johnson, D. L. Koller, D. Lai, Xiaoling Xuei, Howard Edenberg, Siu Hui, Tatiana Foroud, Munro Peacock, Michael Econs

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Abstract

Introduction: Peak bone mineral density (BMD) achieved during adulthood is a major determinant of osteoporotic fracture in later life. Although environmental factors affect peak BMD, it is a highly heritable trait. Recently, bone morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for osteoporotic fractures and low BMD in Icelandic and Danish populations. Methods: To determine whether polymorphisms in the BMP2 gene contribute to BMD variation in our population of healthy American whites, we tested seven single nucleotide polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes in the previous study. BMD at the femoral neck and lumbar spine (L2-L4) were measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18-61) and 1,291 pre-menopausal women (age 20-50). SNP genotypes/ haplotypes were tested for population-based association with BMD using analysis of variance. Results: None of the polymorphisms tested reached statistical significance (all p values >0.05) for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP haplotypes spanning the entire BMP2 gene were marginally associated with BMD in men (p values=0.019-0.043). However, these haplotypes would account for only a small, if any, portion of BMD variation and would not be significant after adjustment for multiple comparisons. Conclusions: These results demonstrate that genetic variations in BMP2 do not substantially contribute to BMD variation in our population of healthy American whites.

Original languageEnglish
Pages (from-to)587-592
Number of pages6
JournalOsteoporosis International
Volume17
Issue number4
DOIs
StatePublished - Apr 2006

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Bone Morphogenetic Protein 2
Bone Density
Genes
Haplotypes
Single Nucleotide Polymorphism
Osteoporotic Fractures
Femur Neck
Population
Spine
Photon Absorptiometry
Analysis of Variance
Genotype
Phenotype

Keywords

  • Bone mineral density
  • Bone morphogenetic protein 2
  • Genetic association
  • Osteoporosis
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone mineral density in white men or women",
abstract = "Introduction: Peak bone mineral density (BMD) achieved during adulthood is a major determinant of osteoporotic fracture in later life. Although environmental factors affect peak BMD, it is a highly heritable trait. Recently, bone morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for osteoporotic fractures and low BMD in Icelandic and Danish populations. Methods: To determine whether polymorphisms in the BMP2 gene contribute to BMD variation in our population of healthy American whites, we tested seven single nucleotide polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes in the previous study. BMD at the femoral neck and lumbar spine (L2-L4) were measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18-61) and 1,291 pre-menopausal women (age 20-50). SNP genotypes/ haplotypes were tested for population-based association with BMD using analysis of variance. Results: None of the polymorphisms tested reached statistical significance (all p values >0.05) for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP haplotypes spanning the entire BMP2 gene were marginally associated with BMD in men (p values=0.019-0.043). However, these haplotypes would account for only a small, if any, portion of BMD variation and would not be significant after adjustment for multiple comparisons. Conclusions: These results demonstrate that genetic variations in BMP2 do not substantially contribute to BMD variation in our population of healthy American whites.",
keywords = "Bone mineral density, Bone morphogenetic protein 2, Genetic association, Osteoporosis, Single nucleotide polymorphism",
author = "S. Ichikawa and Johnson, {M. L.} and Koller, {D. L.} and D. Lai and Xiaoling Xuei and Howard Edenberg and Siu Hui and Tatiana Foroud and Munro Peacock and Michael Econs",
year = "2006",
month = "4",
doi = "10.1007/s00198-005-0018-5",
language = "English",
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pages = "587--592",
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T1 - Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone mineral density in white men or women

AU - Ichikawa, S.

AU - Johnson, M. L.

AU - Koller, D. L.

AU - Lai, D.

AU - Xuei, Xiaoling

AU - Edenberg, Howard

AU - Hui, Siu

AU - Foroud, Tatiana

AU - Peacock, Munro

AU - Econs, Michael

PY - 2006/4

Y1 - 2006/4

N2 - Introduction: Peak bone mineral density (BMD) achieved during adulthood is a major determinant of osteoporotic fracture in later life. Although environmental factors affect peak BMD, it is a highly heritable trait. Recently, bone morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for osteoporotic fractures and low BMD in Icelandic and Danish populations. Methods: To determine whether polymorphisms in the BMP2 gene contribute to BMD variation in our population of healthy American whites, we tested seven single nucleotide polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes in the previous study. BMD at the femoral neck and lumbar spine (L2-L4) were measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18-61) and 1,291 pre-menopausal women (age 20-50). SNP genotypes/ haplotypes were tested for population-based association with BMD using analysis of variance. Results: None of the polymorphisms tested reached statistical significance (all p values >0.05) for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP haplotypes spanning the entire BMP2 gene were marginally associated with BMD in men (p values=0.019-0.043). However, these haplotypes would account for only a small, if any, portion of BMD variation and would not be significant after adjustment for multiple comparisons. Conclusions: These results demonstrate that genetic variations in BMP2 do not substantially contribute to BMD variation in our population of healthy American whites.

AB - Introduction: Peak bone mineral density (BMD) achieved during adulthood is a major determinant of osteoporotic fracture in later life. Although environmental factors affect peak BMD, it is a highly heritable trait. Recently, bone morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for osteoporotic fractures and low BMD in Icelandic and Danish populations. Methods: To determine whether polymorphisms in the BMP2 gene contribute to BMD variation in our population of healthy American whites, we tested seven single nucleotide polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes in the previous study. BMD at the femoral neck and lumbar spine (L2-L4) were measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18-61) and 1,291 pre-menopausal women (age 20-50). SNP genotypes/ haplotypes were tested for population-based association with BMD using analysis of variance. Results: None of the polymorphisms tested reached statistical significance (all p values >0.05) for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP haplotypes spanning the entire BMP2 gene were marginally associated with BMD in men (p values=0.019-0.043). However, these haplotypes would account for only a small, if any, portion of BMD variation and would not be significant after adjustment for multiple comparisons. Conclusions: These results demonstrate that genetic variations in BMP2 do not substantially contribute to BMD variation in our population of healthy American whites.

KW - Bone mineral density

KW - Bone morphogenetic protein 2

KW - Genetic association

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KW - Single nucleotide polymorphism

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