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A common polymorphism rs1800247 in osteocalcin gene is associated with hypertension and diastolic blood pressure levels: the Shanghai Changfeng study

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Abstract

Osteocalcin may have a role in hypertension due to its close relationship with energy metabolism and insulin sensitivity. The aim of this study was to evaluate the association of a common polymorphism rs1800247 in osteocalcin gene with hypertension and related traits. This was a population-based cross-sectional study including 5647 individuals. Baseline information was collected. Body mass index (BMI), waist circumference, blood pressure, glucose and lipids were determined. Homeostasis model assessment for insulin resistance (HOMA-IR) was used to estimate insulin sensitivity. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. The carriers of C allele of rs1800247 were associated with a decreased odds of hypertension compared with the carriers of T allele adjusted for age, sex and BMI (odds ratio (OR)=0.89, 95% confidence interval (CI) 0.81–0.97, P=0.01). The carriers of C allele were also associated with a lower diastolic blood pressure (DBP) level adjusted for age, sex and BMI in normotensive individuals (β=−0.55, 95% CI −0.99 to −0.10, P=0.02), but its association with systolic blood pressure levels was not significant. The interaction between rs1800247 and HOMA-IR on hypertension was significant (P<0.001). In the stratified analysis by the median of HOMA-IR (1.93), rs1800247 was significantly associated with hypertension in the subgroup with HOMA-IR⩽1.93 (OR=0.82, 95% CI 0.71–0.94, P=0.005), but this association was not significant in the subgroup with HOMA-IR >1.93. We demonstrated that a common polymorphism rs1800247 in osteocalcin gene was associated with hypertension and DBP levels. The association of rs1800247 with hypertension was affected by its interaction with HOMA-IR.

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References

  1. Confavreux CB, Levine RL, Karsenty G . A paradigm of integrative physiology, the crosstalk between bone and energy metabolisms. Mol Cell Endocrinol 2009; 310: 21–29.

    Article  CAS  Google Scholar 

  2. Wolf G . Function of the bone protein osteocalcin: definitive evidence. Nutr Rev 1996; 54: 332–333.

    Article  CAS  Google Scholar 

  3. Epstein S . Serum and urinary markers of bone remodeling: assessment of bone turnover. Endocr Rev 1988; 9: 437–449.

    Article  CAS  Google Scholar 

  4. Chen L, Li Q, Yang Z, Ye Z, Huang Y, He M et al. Osteocalcin, glucose metabolism, lipid profile and chronic low-grade inflammation in middle-aged and elderly Chinese. Diabet Med 2013; 30: 309–317.

    Article  CAS  Google Scholar 

  5. Bao Y, Zhou M, Lu Z, Li H, Wang Y, Sun L et al. Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men. Clin Endocrinol (Oxf) 2011; 75: 196–201.

    Article  CAS  Google Scholar 

  6. Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B . Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009; 94: 827–832.

    Article  CAS  Google Scholar 

  7. Kim S, Lee JY, Im JA, Kim DW, Lee HS, Kim SH et al. Association between serum osteocalcin and insulin resistance in postmenopausal, but not premenopausal, women in Korea. Menopause 2013; 20: 1061–1066.

    Article  Google Scholar 

  8. Gower BA, Pollock NK, Casazza K, Clemens TL, Goree LL, Granger WM . Associations of total and undercarboxylated osteocalcin with peripheral and hepatic insulin sensitivity and beta-cell function in overweight adults. J Clin Endocrinol Metab 2013; 98: E1173–E1180.

    Article  CAS  Google Scholar 

  9. Polgreen LE, Jacobs DR Jr., Nathan BM, Steinberger J, Moran A, Sinaiko AR . Association of osteocalcin with obesity, insulin resistance, and cardiovascular risk factors in young adults. Obesity (Silver Spring) 2012; 20: 2194–2201.

    Article  CAS  Google Scholar 

  10. Bao Y, Ma X, Yang R, Wang F, Hao Y, Dou J et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J Clin Endocrinol Metab 2013; 98: 345–351.

    Article  CAS  Google Scholar 

  11. Lee SW, Jo HH, Kim MR, You YO, Kim JH . Association between obesity, metabolic risks and serum osteocalcin level in postmenopausal women. Gynecol Endocrinol 2012; 28: 472–477.

    Article  CAS  Google Scholar 

  12. Lenders CM, Lee PD, Feldman HA, Wilson DM, Abrams SH, Gitelman SE et al. A cross-sectional study of osteocalcin and body fat measures among obese adolescents. Obesity (Silver Spring) 2013; 21: 808–814.

    Article  CAS  Google Scholar 

  13. Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L et al. Insulin resistance in essential hypertension. N Engl J Med 1987; 317: 350–357.

    Article  CAS  Google Scholar 

  14. Reaven GM . Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–1607.

    Article  CAS  Google Scholar 

  15. Mathieu P, Poirier P, Pibarot P, Lemieux I, Despres JP . Visceral obesity: the link among inflammation, hypertension, and cardiovascular disease. Hypertension 2009; 53: 577–584.

    Article  CAS  Google Scholar 

  16. Tan A, Gao Y, Yang X, Zhang H, Qin X, Mo L et al. Low serum osteocalcin level is a potential marker for metabolic syndrome: results from a Chinese male population survey. Metabolism 2011; 60: 1186–1192.

    Article  CAS  Google Scholar 

  17. Bae SJ, Choe JW, Chung YE, Kim BJ, Lee SH, Kim HY et al. The association between serum osteocalcin levels and metabolic syndrome in Koreans. Osteoporos Int 2011; 22: 2837–2846.

    Article  CAS  Google Scholar 

  18. Oosterwerff MM, van Schoor NM, Lips P, Eekhoff EM . Osteocalcin as a predictor of the metabolic syndrome in older persons: a population-based study. Clin Endocrinol (Oxf) 2013; 78: 242–247.

    Article  CAS  Google Scholar 

  19. Kamdem LK, Hamilton L, Cheng C, Liu W, Yang W, Johnson JA et al. Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia. Pharmacogenet Genomics 2008; 18: 507–514.

    Article  CAS  Google Scholar 

  20. Yamada Y, Ando F, Niino N, Shimokata H . Association of polymorphisms of interleukin-6, osteocalcin, and vitamin D receptor genes, alone or in combination, with bone mineral density in community-dwelling Japanese women and men. J Clin Endocrinol Metab 2003; 88: 3372–3378.

    Article  CAS  Google Scholar 

  21. Kim JG, Ku SY, Lee DO, Jee BC, Suh CS, Kim SH et al. Relationship of osteocalcin and matrix Gla protein gene polymorphisms to serum osteocalcin levels and bone mineral density in postmenopausal Korean women. Menopause 2006; 13: 467–473.

    Article  Google Scholar 

  22. Gao X, Hofman A, Hu Y, Lin H, Zhu C, Jeekel J et al. The Shanghai Changfeng Study: a community-based prospective cohort study of chronic diseases among middle-aged and elderly: objectives and design. Eur J Epidemiol 2010; 25: 885–893.

    Article  Google Scholar 

  23. Garaulet M, Perex-Llamas F, Fuente T, Zamora S, Tebar FJ . Anthropometric, computed tomography and fat cell data in an obese population: relationship with insulin, leptin, tumor necrosis factor-alpha, sex hormone-binding globulin and sex hormones. Eur J Endocrinol 2000; 143: 657–666.

    Article  CAS  Google Scholar 

  24. Bao Y, Lu J, Wang C, Yang M, Li H, Zhang X et al. Optimal waist circumference cutoffs for abdominal obesity in Chinese. Atherosclerosis 2008; 201: 378–384.

    Article  CAS  Google Scholar 

  25. Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    CAS  Google Scholar 

  26. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  27. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206–1252.

    Article  CAS  Google Scholar 

  28. McGuigan F, Kumar J, Ivaska KK, Obrant KJ, Gerdhem P, Akesson K . Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification. J Bone Miner Res 2010; 25: 1392–1399.

    Article  CAS  Google Scholar 

  29. Xu H, Xiao W, Luo D, Liu YM, Zou L, Kuang HB . Association analysis of genetic polymorphisms and potential interaction of the osteocalcin (BGP) and ER-alpha genes with body mass index (BMI) in premenopausal Chinese women. Acta Pharmacol Sin 2010; 31: 455–460.

    Article  CAS  Google Scholar 

  30. Sowers M, Willing M, Burns T, Deschenes S, Hollis B, Crutchfield M et al. Genetic markers, bone mineral density, and serum osteocalcin levels. J Bone Miner Res 1999; 14: 1411–1419.

    Article  CAS  Google Scholar 

  31. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD . Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994; 94: 1172–1179.

    Article  CAS  Google Scholar 

  32. DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ . The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 1975; 55: 845–855.

    Article  CAS  Google Scholar 

  33. Lastra G, Dhuper S, Johnson MS, Sowers JR . Salt, aldosterone, and insulin resistance: impact on the cardiovascular system. Nat Rev Cardiol 2010; 7: 577–584.

    Article  CAS  Google Scholar 

  34. Mo XY, Cao CK, Xu FH, Liu MY, Li MX, Qin YJ et al. Lack of association between the HindIII RFLP of the osteocalcin (BGP) gene and bone mineral density (BMD) in healthy pre- and postmenopausal Chinese women. J Bone Miner Metab 2004; 22: 264–269.

    Article  CAS  Google Scholar 

  35. Lei SF, Zhang YY, Deng FY, Liu MY, Liu XH, Zhou XG et al. Bone mineral density and five prominent candidate genes in Chinese men: associations, interaction effects and their implications. Maturitas 2005; 51: 199–206.

    Article  CAS  Google Scholar 

  36. Jiang DK, Xu FH, Liu MY, Chen XD, Li MX, Liu YJ et al. No evidence of association of the osteocalcin gene HindIII polymorphism with bone mineral density in Chinese women. J Musculoskelet Neuronal Interact 2007; 7: 149–154.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by the following grants: the National Key Basic Research Program of China (Grant No. 2012CB524906 and Grant No. 2011CB504004 to XG; http://www.973.gov.cn/Default_3.aspx), the Major Project of Shanghai Bureau of Health (Grant No. 12GWZX0103 and Grant No. 13ZYJB0802 to XG), the Project of Shanghai Bureau of Health (Grant No. 20124242 to YL), and National Natural Science Foundation of China (Grant No. 81402207 to YL).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China

    Y Ling, X Gao & H Lin

  2. Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China

    H Ma

  3. Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China

    B Pan

  4. Department of Clinical Nutrition, Zhongshan Hospital, Fudan University, Shanghai, China

    J Gao

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  1. Y Ling
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Correspondence to X Gao.

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Ling, Y., Gao, X., Lin, H. et al. A common polymorphism rs1800247 in osteocalcin gene is associated with hypertension and diastolic blood pressure levels: the Shanghai Changfeng study. J Hum Hypertens 30, 679–684 (2016). https://doi.org/10.1038/jhh.2016.16

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