Relationships between endothelial nitric oxide synthase gene polymorphisms and osteoporosis in postmenopausal women
Open accessAbstract
OBJECTIVE: To investigate the relationships between endothelial nitric oxide synthases (eNOS) G894T and 27 bp-variable number tandem repeat (VNTR) gene polymorphisms and osteoporosis in the postmenopausal women of Chinese Han nationality. METHODS: In the present study, 281 postmenopausal women from Xi'an urban area in West China were recruited, and divided into osteoporosis, osteopenia, and normal groups according to the diagnostic criteria of osteoporosis proposed by World Health Organization (WHO). The bone mineral density (BMD) values of lumbar vertebrae and left hips were determined by QDR-2000 dual energy X-ray absorptiometry. Blood samples were tested for plasma biochemical indicators including testosterone, estradiol, calcitonin, osteocalcin, and procollagen type I amino-terminal propeptide by enzyme-linked immunosorbent assay (ELISA), tartrate-resistant acid phosphatase by spectrophotometric method, and the content of nitric oxide by Griess method. Genome DNA was extracted from whole blood, and G894T polymorphism of eNOS gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and 27 bp-VNTR polymorphism of eNOS gene was genotyped by PCR method. Then the relationships between genotypes and biochemical indicators, genotypes and osteoporosis, and haplotypes and osteoporosis were analyzed. RESULTS: The average BMD values of the femoral neck, ward's triangle and lumbar vertebrae 1-4 (L1-L4) in the subjects with T/T genotype in eNOS G894T locus were significantly higher than those in the subjects with G/T and G/G genotypes (P<0.05). The average BMD of the femoral neck in the subjects with a/a genotype of eNOS 27 bp-VNTR locus was evidently higher than that in the subjects with b/b genotype (P<0.05). The plasma testosterone and osteocalcin concentrations in the subjects of eNOS G894T G/T genotype were evidently higher than those in the subjects of other genotypes (P<0.05); the plasma estradiol concentration in the subjects of eNOS 27 bp-VNTR a/a genotype was obviously higher than that in the subjects of b/b genotype (P<0.01). eNOS G/G homozygous frequencies in osteoporosis women, osteopenia women, and normal women were 85.37%, 76.38%, and 83.87%, respectively (P>0.05). 0% osteoporosis woman, 0.79% osteopenia women, and 3.23% normal women were eNOS a/a homozygous (P<0.05). The frequencies of eNOS 27 bp-VNTR a allele were 5.33% in the osteoporosis group, 10.24% in the osteopenia group, and 16.13% in the normal group (P<0.05, odds ratio (OR)=0.29, 95% confidence interval (CI)=0.11-0.77), suggesting that a/a genotype and a allele might have protective effects on osteoporosis. The haplotype analysis showed that G-b was 87.7% (214/244) in the osteoporosis group (P<0.05, OR=2.48, 95% CI=1.18-5.18). G-a was 5.3% (13/244) in the osteoporosis group (P<0.05, OR=0.29, 95% CI=0.11-0.77). G-b was a risk factor for osteoporosis, and G-a a protective factor. CONCLUSION: eNOS G894T G/T genotype influenced the plasma testosterone and osteocalcin concentrations, and T/T genotype influenced BMD. eNOS 27 bp-VNTR a/a genotype increased plasma estradiol concentration to have a protective effect on osteoporosis.
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eNOS plays an important role in regulating osteoblast activity and bone formation, because eNOS knockout mice exhibit osteoporosis due to defective bone formation, and eNOS gene polymorphisms were reported to be causally linked to osteoporosis in postmenopausal women.
“On the other hand, eNOS, a constitutive NO synthase, plays an important role in regulating osteoblast activity and bone formation, because eNOS knockout mice exhibit osteoporosis due to defective bone formation, and eNOS gene polymorphisms were reported to be causally linked to osteoporosis in postmenopausal women [159].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [159]
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- Liu, S.Z., Yan, H., Xu, P., Hou, B., Zhuang, G.H., Zeng, Y.H., Guo, X., Lu, S.M., 2008. Correlational analysis between bone mineral density and physiological characters of postmenopausal women in Xi'an urban area. Journal of Xi'an Jiaotong University (Medical Sciences), 29(1): 107-109 (in Chinese).
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- Authors
- Liu, S.-Z., Yan, H., Hou, W.-K., Xu, P., Tian, J., Tian, L.-F., Zhu, B.-F., Ma, J., & Lu, S.-M.
- Affiliations
- Xi'an Jiaotong University (CN)
- Xi'an Honghui Hospital (CN)
- Corresponding author
- Yan, Hong
- Venue
- Journal of Zhejiang University SCIENCE B
- Publisher
- Zhejiang University Press
- Published
- 2009-07-30
- Volume
- 10
- Issue
- 8
- Pages
- 609-618
- ISSN
- 1673-1581 (ISSN-L)
- 1862-1783
- PMC
- PMC2722703
- OpenAlex
- W2070063868
- Cited by
- 18
- References
- 61
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Zhejiang University SCIENCE B (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30630058)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- endothelial nitric oxide synthase, eNOS gene polymorphism, osteoporosis, postmenopausal women, G894T polymorphism, bone mineral density, haplotypes, testosterone, estradiol, osteocalcin, nitric oxide, genetic susceptibility, Han Chinese women, osteopenia
- MeSH terms
- Aged, Female, Gene Frequency, Genotype, Haplotypes, Humans, Middle Aged, Nitric Oxide, Polymorphism, Genetic, Testosterone, Bone Density, Osteoporosis, Postmenopausal, Osteocalcin, Minisatellite Repeats, Nitric Oxide Synthase Type III
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