Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population

T. H. Kim, J. M. Hong, J. Y. Lee, B. Oh, E. K. Park, C. K. Lee, Sang Cheol Bae, S. Y. Kim

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Objective: Disruption of the vascular supply to the bone and subsequent hypoxia has been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Vascular endothelial growth factor (VEGF), a major inducer of angiogenesis, has been correlated with several pathological conditions, from inflammation to ischemic processes. A number of polymorphisms in the VEGF gene have been described as being associated with several diseases, such as diabetic retinopathy, prostate cancer and breast cancer. The aim of this study was to evaluate the association of VEGF gene polymorphisms with ONFH in a case-control study. Methods: Three polymorphisms (-2578C>A, -634G>C and +936C>T) in VEGF were genotyped in 317 ONFH patients and 497 control subjects, using the TaqMan 5′ allelic discrimination assay. We performed the association analysis of genotyped single nucleotide polymorphisms (SNPs) and haplotypes with ONFH. Results: The -634G>C genotype was significantly associated with an increased risk for ONFH in dominant model with odds ratio (OR) of 1.47, 95% confidence intervals (CIs) 1.08-2.01 with P value 0.015. Further analysis stratified by sex showed that the -634G>C genotype was also significantly associated with a high risk for male patients considering the dominant model with OR of 1.60, 95% CI 1.13-2.26 with P value 0.008. Haplotype association analysis did not provide a further delineation of the risk allele. Conclusion: Our study is, to our knowledge, the first report that shows the -634G>C polymorphism in the VEGF promoter was associated with an increased susceptibility of ONFH in the Korean population.

Original languageEnglish
Pages (from-to)287-291
Number of pages5
JournalOsteoarthritis and Cartilage
Volume16
Issue number3
DOIs
StatePublished - 2008 Mar 1

Fingerprint

Osteonecrosis
Thigh
Polymorphism
Vascular Endothelial Growth Factor A
Genes
Population
Association reactions
Haplotypes
Odds Ratio
Genotype
Confidence Intervals
Breast Neoplasms
Nucleotides
Angiogenesis Inducing Agents
Diabetic Retinopathy
Assays
Bone
Single Nucleotide Polymorphism
Blood Vessels
Intercellular Signaling Peptides and Proteins

Keywords

  • Angiogenesis
  • Haplotypes
  • Linkage disequilibrium (LD)
  • Osteonecrosis of the femoral head (ONFH)
  • Polymorphism
  • Vascular endothelial growth factor (VEGF)

Cite this

Kim, T. H. ; Hong, J. M. ; Lee, J. Y. ; Oh, B. ; Park, E. K. ; Lee, C. K. ; Bae, Sang Cheol ; Kim, S. Y. / Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population. In: Osteoarthritis and Cartilage. 2008 ; Vol. 16, No. 3. pp. 287-291.
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title = "Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population",
abstract = "Objective: Disruption of the vascular supply to the bone and subsequent hypoxia has been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Vascular endothelial growth factor (VEGF), a major inducer of angiogenesis, has been correlated with several pathological conditions, from inflammation to ischemic processes. A number of polymorphisms in the VEGF gene have been described as being associated with several diseases, such as diabetic retinopathy, prostate cancer and breast cancer. The aim of this study was to evaluate the association of VEGF gene polymorphisms with ONFH in a case-control study. Methods: Three polymorphisms (-2578C>A, -634G>C and +936C>T) in VEGF were genotyped in 317 ONFH patients and 497 control subjects, using the TaqMan 5′ allelic discrimination assay. We performed the association analysis of genotyped single nucleotide polymorphisms (SNPs) and haplotypes with ONFH. Results: The -634G>C genotype was significantly associated with an increased risk for ONFH in dominant model with odds ratio (OR) of 1.47, 95{\%} confidence intervals (CIs) 1.08-2.01 with P value 0.015. Further analysis stratified by sex showed that the -634G>C genotype was also significantly associated with a high risk for male patients considering the dominant model with OR of 1.60, 95{\%} CI 1.13-2.26 with P value 0.008. Haplotype association analysis did not provide a further delineation of the risk allele. Conclusion: Our study is, to our knowledge, the first report that shows the -634G>C polymorphism in the VEGF promoter was associated with an increased susceptibility of ONFH in the Korean population.",
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Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population. / Kim, T. H.; Hong, J. M.; Lee, J. Y.; Oh, B.; Park, E. K.; Lee, C. K.; Bae, Sang Cheol; Kim, S. Y.

In: Osteoarthritis and Cartilage, Vol. 16, No. 3, 01.03.2008, p. 287-291.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population

AU - Kim, T. H.

AU - Hong, J. M.

AU - Lee, J. Y.

AU - Oh, B.

AU - Park, E. K.

AU - Lee, C. K.

AU - Bae, Sang Cheol

AU - Kim, S. Y.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Objective: Disruption of the vascular supply to the bone and subsequent hypoxia has been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Vascular endothelial growth factor (VEGF), a major inducer of angiogenesis, has been correlated with several pathological conditions, from inflammation to ischemic processes. A number of polymorphisms in the VEGF gene have been described as being associated with several diseases, such as diabetic retinopathy, prostate cancer and breast cancer. The aim of this study was to evaluate the association of VEGF gene polymorphisms with ONFH in a case-control study. Methods: Three polymorphisms (-2578C>A, -634G>C and +936C>T) in VEGF were genotyped in 317 ONFH patients and 497 control subjects, using the TaqMan 5′ allelic discrimination assay. We performed the association analysis of genotyped single nucleotide polymorphisms (SNPs) and haplotypes with ONFH. Results: The -634G>C genotype was significantly associated with an increased risk for ONFH in dominant model with odds ratio (OR) of 1.47, 95% confidence intervals (CIs) 1.08-2.01 with P value 0.015. Further analysis stratified by sex showed that the -634G>C genotype was also significantly associated with a high risk for male patients considering the dominant model with OR of 1.60, 95% CI 1.13-2.26 with P value 0.008. Haplotype association analysis did not provide a further delineation of the risk allele. Conclusion: Our study is, to our knowledge, the first report that shows the -634G>C polymorphism in the VEGF promoter was associated with an increased susceptibility of ONFH in the Korean population.

AB - Objective: Disruption of the vascular supply to the bone and subsequent hypoxia has been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Vascular endothelial growth factor (VEGF), a major inducer of angiogenesis, has been correlated with several pathological conditions, from inflammation to ischemic processes. A number of polymorphisms in the VEGF gene have been described as being associated with several diseases, such as diabetic retinopathy, prostate cancer and breast cancer. The aim of this study was to evaluate the association of VEGF gene polymorphisms with ONFH in a case-control study. Methods: Three polymorphisms (-2578C>A, -634G>C and +936C>T) in VEGF were genotyped in 317 ONFH patients and 497 control subjects, using the TaqMan 5′ allelic discrimination assay. We performed the association analysis of genotyped single nucleotide polymorphisms (SNPs) and haplotypes with ONFH. Results: The -634G>C genotype was significantly associated with an increased risk for ONFH in dominant model with odds ratio (OR) of 1.47, 95% confidence intervals (CIs) 1.08-2.01 with P value 0.015. Further analysis stratified by sex showed that the -634G>C genotype was also significantly associated with a high risk for male patients considering the dominant model with OR of 1.60, 95% CI 1.13-2.26 with P value 0.008. Haplotype association analysis did not provide a further delineation of the risk allele. Conclusion: Our study is, to our knowledge, the first report that shows the -634G>C polymorphism in the VEGF promoter was associated with an increased susceptibility of ONFH in the Korean population.

KW - Angiogenesis

KW - Haplotypes

KW - Linkage disequilibrium (LD)

KW - Osteonecrosis of the femoral head (ONFH)

KW - Polymorphism

KW - Vascular endothelial growth factor (VEGF)

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