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Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.8 P.609-618

http://doi.org/10.1631/jzus.B0920137


Relationships between endothelial nitric oxide synthase gene polymorphisms and osteoporosis in postmenopausal women


Author(s):  Shun-zhi LIU, Hong YAN, Wei-kun HOU, Peng XU, Juan TIAN, Li-fang TIAN, Bo-feng ZHU, Jie MA, She-min LU

Affiliation(s):  Department of Public Health, School of Medicine, Xi’ more

Corresponding email(s):   yanhonge@mail.xjtu.edu.cn, lushemin@mail.xjtu.edu.cn

Key Words:  Postmenopausal women, Osteoporosis, Endothelial nitric oxide synthase, Gene polymorphisms, Bone mineral density


Shun-zhi LIU, Hong YAN, Wei-kun HOU, Peng XU, Juan TIAN, Li-fang TIAN, Bo-feng ZHU, Jie MA, She-min LU. Relationships between endothelial nitric oxide synthase gene polymorphisms and osteoporosis in postmenopausal women[J]. Journal of Zhejiang University Science B, 2009, 10(8): 609-618.

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author="Shun-zhi LIU, Hong YAN, Wei-kun HOU, Peng XU, Juan TIAN, Li-fang TIAN, Bo-feng ZHU, Jie MA, She-min LU",
journal="Journal of Zhejiang University Science B",
volume="10",
number="8",
pages="609-618",
year="2009",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0920137"
}

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%T Relationships between endothelial nitric oxide synthase gene polymorphisms and osteoporosis in postmenopausal women
%A Shun-zhi LIU
%A Hong YAN
%A Wei-kun HOU
%A Peng XU
%A Juan TIAN
%A Li-fang TIAN
%A Bo-feng ZHU
%A Jie MA
%A She-min LU
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%V 10
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%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0920137

TY - JOUR
T1 - Relationships between endothelial nitric oxide synthase gene polymorphisms and osteoporosis in postmenopausal women
A1 - Shun-zhi LIU
A1 - Hong YAN
A1 - Wei-kun HOU
A1 - Peng XU
A1 - Juan TIAN
A1 - Li-fang TIAN
A1 - Bo-feng ZHU
A1 - Jie MA
A1 - She-min LU
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 8
SP - 609
EP - 618
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0920137


Abstract: 
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.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1] Aguirre, J., Buttery, L., O'Shaughnessy, M., Afzal, F., Fernandez de Marticorena, I., Hukkanen, M., Huang, P., MacIntyre, I., Polak, J., 2001. Endothelial nitric oxide synthase gene-deficient mice demonstrate marked retardation in postnatal bone formation, reduced bone volume, and defects in osteoblast maturation and activity. The American Journal of Pathology, 158(1):247-257.

[2] Alexandre, C., 2005. Androgens and bone metabolism. Joint Bone Spine, 72(3):202-206.

[3] Antoniades, C.A., Tousoulis, D., Vasiliadou, C., Pitsavos, C., Marinou, K., Stefanadi, E., Koumallos, N., Toulouzas, K., Siasos, G., Chrysochoou, C., et al., 2007. Genetic polymorphism G894T on eNOS gene increases the smoking-associated risk for premature myocardial infarction: a gene-environment interaction. Journal of the American College of Cardiology, 49(9):336a-336a.

[4] Armour, K.E., Armour, K.J., Gallagher, M.E., Gödecke, A., Helfrich, M.H., Reid, D.M., Ralston, S.H., 2001. Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase. Endocrinology, 142(2): 760-766.

[5] Benjafield, A.V., Morris, B.J., 2000. Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension. American Journal of Hypertension, 13(9):994-998.

[6] Blair, M.W., Pedraza, F., Buendia, H.F., Gaitan-Solis, E., Beebe, S.E., Gepts, P., Tohme, J., 2003. Development of a genome-wide anchored microsatellite map for common bean (Phaseolus vulgaris L.). TAG Theoretical and Applied Genetics, 107(8):1362-1374.

[7] Brennan, P.A., Sharma, S., Bowden, J.R., Umar, T., 2003. Expression of inducible nitric oxide synthase in bone metastases. European Journal of Surgical Oncology, 29(7):619-623.

[8] Cho, K., Demissie, S., Dupuis, J., Cupples, L.A., Kathiresan, S., Beck, T.J., Karasik, D., Kiel, D.P., 2008. Polymorphisms in the endothelial nitric oxide synthase gene and bone density/ultrasound and geometry in humans. Bone, 42(1):53-60.

[9] Cicinelli, E., Ignarro, D.J., Lograno, M., Galantino, P., Balzano, G., Schonauer, L.M., 1996. Circulating levels of nitric oxide in fertile women in relation to the menstrual cycle. Fertility and Sterility, 66(6):1036-1038.

[10] Firat, S.C., Cetin, Z., Samanci, N., Aydin, F., Balci, N., Gungor, F., Firat, M.Z., Luleci, G., Karauzum, S.B., 2009. Evaluation of eNOS gene polymorphisms in relation to BMD in postmenopausal women. Maturitas, in press.

[11] Gambacciani, M., Vacca, F., 2004. Postmenopausal osteoporosis and hormone replacement therapy. Minerva Medica, 95(6):507-520.

[12] Grassi, F., Fan, X., Rahnert, J., Weitzmann, M.N., Pacifici, R., Nanes, M.S., Rubin, J., 2006. Bone re/modeling is more dynamic in the endothelial nitric oxide synthase(–/–) mouse. Endocrinology, 147(9):4392-4399.

[13] Haas, M.L., Moore, K., 2007. Osteoporosis: an invisible, undertreated, and neglected disease of elderly men. Journal of Elder Abuse & Neglect, 19(1):61-73.

[14] Hoffmann, I.S., Tavares-Mordwinkin, R., Castejon, A.M., Alfieri, A.B., Cubeddu, L.X., 2005. Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. Journal of Human Hypertension, 19:233-240.

[15] Ilich, J.Z., Kerstetter, J.E., 2000. Nutrition in bone health revisited: a story beyond calcium. Journal of the American College of Nutrition, 19(6):715-737.

[16] Imashuku, Y., Takada, M., Murata, K., 2007. Comparisons of bone mass measurements on various skeletal sites including quantitative ultrasonography of the calcaneus for assessing age-related losses, their correlations, and diagnostic agreement using the Japanese and WHO criteria for osteoporosis. Radiation medicine, 25(4):148-154.

[17] Kozak, W., Kozak, A., 2003. Genetic models in applied physiology. Differential role of nitric oxide synthase isoforms in fever of different etiologies: studies using Nos gene-deficient mice. Journal of Applied Physiology, 94(6):2534-2544.

[18] Lee, A.J., Hodges, S., Eastell, R., 2000. Measurement of osteocalcin. Annals of Clinical Biochemistry, 37(Pt 4): 432-446.

[19] Lee, Y.C., Huang, C.H., Wang, C.J., Liu, C.C., Wu, W.J., Chang, L.L., Lin, H.H., 2007. The associations among eNOS G894T gene polymorphism, erectile dysfunction and related risk factors. BJU international, 100(5): 1116-1120.

[20] Lewiecki, E.M., 2008. Prevention and treatment of postmenopausal osteoporosis. Obstetrics and Gynecology Clinics of North America, 35(2):301-315.

[21] Li, D.B., Hua, Q., Pi, L., 2005. Synergistic effect between eNOS gene G894T and GNB3 gene C825T polymorphisms in patients with essential hypertension. American Journal of Hypertension, 18(5):163a.

[22] 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).

[23] Liu, S.Z., Yan, H., Xu, P., Li, J.P., Zhuang, G.H., Zhu, B.F., Lu, S.M., 2009. Correlation analysis between bone mineral density and serum element contents of postmenopausal women in Xi’an urban area. Biological Trace Element Research, in press.

[24] Liu, Z., Piao, J., Pang, L., Qing, X., Nan, S., Pan, Z., Guo, Y., Wang, X., Li, F., Liu, J., Cheng, X., 2002. The diagnostic criteria for primary osteoporosis and the incidence of osteoporosis in China. Journal of Bone and Mineral Metabolism, 20(4):181-189.

[25] Ma, J., Qin, W., Wang, X.Y., Guo, T.W., Bian, L., Duan, S.W., Li, X.W., Zou, F.G., Fang, Y.R., Fang, J.X., et al., 2006. Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations. Molecular Psychiatry, 11(5):479-487.

[26] Malone, G., Peskemm, S.T., Zimmer, P.D., Malone, E., Meneghello, G.E., de Oliveira, A.C., 2008. Single nucleotide polymorphism (SNP) detection in the red rice alpha-amylase gene amy1: effect on seedling vigour. Seed Science and Technology, 36:447-455.

[27] Manios, Y., Moschonis, G., Trovas, G., Lyritis, G.P., 2007. Changes in biochemical indexes of bone metabolism and bone mineral density after a 12-mo dietary intervention program: the postmenopausal health study. American Society for Nutrition, 86(3):781-789.

[28] Matyar, S., Attila, G., Acartürk, E., Akpinar, O., Inal, T., 2005. eNOS gene intron 4 a/b VNTR polymorphism is a risk factor for coronary artery disease in Southern Turkey. Clinica Chimica Acta, 354(1-2):153-158.

[29] Mearin, F., García-González, M.A., Strunk, M., Zárate, N., Malagelada, J.R., Lanas, A., 2006. Association between achalasia and nitric oxide synthase gene polymorphisms. The American Journal of Gastroenterology, 101(9): 1979-1984.

[30] Miller, P.D., 2006. Guidelines for the diagnosis of osteoporosis: T-scores vs fractures. Reviews in Endocrine & Metabolic Disorders, 7(1-2):75-89.

[31] Mutlu, M., Argun, M., Kilic, E., Saraymen, R., Yazar, S., 2007. Magnesium, zinc and copper status in osteoporotic, osteopenic and normal post-menopausal women. The Journal of International Medical Research, 35(5): 692-695.

[32] Ongphiphadhanakul, B., 2007. Osteoporosis: the role of genetics and the environment. Forum of Nutrition, 60: 158-167.

[33] Ozgocmen, S., Kaya, H., Fadillioglu, E., Aydogan, R., Yilmaz, Z., 2007. Role of antioxidant systems, lipid peroxidation, and nitric oxide in postmenopausal osteoporosis. Molecular and Cellular Biochemistry, 295(1-2):45-52.

[34] Pocock, N.A., Eisman, J.A., Hopper, J.L., Yeates, M.G., Sambrook, P.N., Eberl, S., 1987. Genetic determinants of bone mass in adults. A twin study. The Journal of Clinical Investigation, 80(3):706-710.

[35] Prentice, A., 2004. Diet, nutrition and the prevention of osteoporosis. Public Health Nutrition, 7(1A):227-243.

[36] Ralston, S.H., 2007. Genetics of osteoporosis. Proceedings of the Nutrition Society, 66(2):158-165.

[37] Reali, M., Frangiskakis, J.M., Grimley, S., Hanley-Yanez, K., Gutmann, R., Dudley, S.C., Ellinor, P.T., Weiss, R., Shalaby, A.A., London, B., McNamara, D.M., 2008. NOS3 Asp298Glu polymorphism and the risk of ventricular arrhythmias in subjects with ICDs: results front GRADE. Journal of Cardiac Failure, 14(6):S42.

[38] Ricciardolo, F.L., Nijkamp, F.P., Folkerts, G., 2006. Nitric oxide synthase (NOS) as therapeutic target for asthma and chronic obstructive pulmonary disease. Current Drug Targets, 7(6):721-735.

[39] Riggs, B.L., Khoslam, S., Atkinson, E.J., Dunstan, C.R., Melton, L.J.3rd, 2003. Evidence that type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency. Osteoporosis International, 14(9):728-733.

[40] Rosselli, M., Imthurn, B., Keller, P.J., Jackson, E.K., Dubey, R.K., 1995. Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol and norethisterone acetate. A two-year follow-up study. Hypertension, 25(4 Pt 2):848-853.

[41] Shah, S.H., 2007. Gene polymorphisms and susceptibility to coronary artery disease. Pediatric Blood Cancer, 48(7): 738-741.

[42] Smith, D.M., Nance, W.E., Kang, K.W., Christian, J.C., Johnston, C.C.Jr., 1973. Genetic factors in determining bone mass. The Journal of Clinical Investigation, 52(11): 2800-2808.

[43] Smith, E.M., Baillie, J.K., Thompson, A.A., Irving, J.B., Porteous, D., Webb, D.J., 2006. Endothelial nitric oxide synthase polymorphisms do not influence pulmonary artery systolic pressure at altitude. High Altitude Medicine & Biology, 7(3):221-227.

[44] Sun, W.L., Chen, L.L., Yan, J., Yu, Z.S., 2005. Effects of IGF-II on promoting proliferation and regulating nitric oxide synthase gene expression in mouse osteoblast-like cell. Journal of Zhejiang University SCIENCE B, 6(7): 699-704.

[45] Tang, W.R., Yang, Y., Wang, B., Xiao, C.J., 2008. Association between a G894T polymorphism of eNOS gene and essential hypertension in Hani and Yi minority groups of China. Archives of Medical Research, 39(2):222-225.

[46] Taylor, B.C., Schreiner, P.J., Zmuda, J.M., Li, J., Moffett, S.P., Beck, T.J., Cummings, S.R., Lee, J.M., Walker, K., Ensrud, K.E., for the SOF Research Group, 2006. Association of endothelial nitric oxide synthase genotypes with bone mineral density, bone loss, hip structure, and risk of fracture in older women: the SOF study. Bone, 39(1): 174-180.

[47] Tok, E.C., Ertunc, D., Oz, U., Camdeviren, H., Ozdemir, G., Dilek, S., 2004. The effect of circulating androgens on bone mineral density in postmenopausal women. Maturitas, 48(3):235-242.

[48] Uthra, S., Raman, R., Mukesh, B.N., Kumari, P., Paul, P.G., Lakshmipathy, P., Gnanamoorthy, P., Sharma, T., McCarty, C.A., Kumaramanickavel, G., 2007. Intron 4 VNTR of endothelial nitric oxide synthase (eNOS) gene and diabetic retinopathy in type 2 patients in southern India. Ophthalmic Genetics, 28(2):77-81.

[49] van't Hof, R.J., Ralston, S.H., 2001. Nitric oxide and bone. Immunology, 103(3):255-261.

[50] van't Hof, R.J., Macphee, J., Libouban, H., Helfrich, M.H., Ralston, S.H., 2004. Regulation of bone mass and bone turnover by neuronal nitric oxide synthase. Endocrinology, 145(11):5068-5074.

[51] Via, M., González-Pérez, E., Esteban, E., López-Alomar, A., Vacca, L., Vona, G., Dugoujon, J.M,, Harich, N,, Moral, P., 2003. Molecular variation in endothelial nitric oxide synthase gene (eNOS) in western Mediterranean populations. Collegium Antropologicum, 7(1):117-124.

[52] Walker, J., 2008. Osteoporosis: pathogenesis, diagnosis and management. Nursing Standard (Royal College of Nursing (Great Britain): 1987), 22(17):48-56.

[53] Williams, F.M., Spector, T.D., 2006. Recent advances in the genetics of osteoporosis. Journal of Musculoskeletal & Neuronal Interactions, 6(1):27-35.

[54] Williams, F.M., Spector, T.D., 2007. The genetics of osteoporosis. Acta Reumatológica Portuguesa, 32(3): 231-240.

[55] Wimalawansa, S.J., 2008. Nitric oxide: novel therapy for osteoporosis. Expert Opinion on Pharmacotherapy, 9(17):3025-3044.

[56] Yang, J.W., Jang, W.S., Hong, S.D., Ji, Y.I., Kim, D.H., Park, J., Kim, S.W., Joung, Y.S., 2008. A case-control association study of the polymorphism at the promoter region of the DRD4 gene in Korean boys with attention deficit-hyperactivity disorder: evidence of association with the –521 C/T SNP. Progress in Neuro-psychopharm-acology & Biological Psychiatry, 32(1):243-248.

[57] Zhang, Q., Allen, S.K., Reece, K.S., 2005. Genetic variation in wild and hatchery stocks of suminoe oyster (Crassostrea ariakensis) assessed by PCR-RFLP and microsatellite markers. Marine Biotechnology (NY), 7(6):588-599.

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