Q J Med 2002; 95: 787-796
© 2002 Association of Physicians
Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders?
From the Departments of 1 Clinical Biochemistry, 2 Diabetes and Metabolic Medicine and 3 Haematology, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London and 4 Department of Cardiology, ‘Barts and The London’ NHS Trust, London, UK
Received 28 February 2002 Accepted for publication 17 May 2002.
Background: Vitamin-D deficiency and vitamin-D receptor genotype (VDR) are risk factors for several disorders with inflammatory components, including coronary heart disease (CHD) and diabetes, though the mechanisms involved are unclear.
Aim: To examine the hypothesis that vitamin D status modulates the matrix metalloproteinase (MMP) system in a population with a high prevalence of vitamin D deficiency, a situation affecting susceptibility to CHD and diabetes.
Design: Prospective cross-sectional, interventional and embedded studies.
Methods: Circulating MMP2,9, the inhibitor TIMP-1 and C-reactive protein (CRP) were measured during studies of vitamin-D deficiency as a risk factor for type 2 diabetes and CHD in 171 healthy British Bangladeshi adults, free of known diabetes or major illness. Vitamin D status, VDR genotype, body-build, blood pressure, lipid and insulin profiles, glucose tolerance, fibrinogen, PAI-1, folate and homocysteine were measured. Vitamin-D-deficient subjects were re-assessed after 1 years' supplementation. MMP, TIMP-1 and CRP levels were measured in 41 subjects halfway through 5-year follow-up. Independent determinants of circulating concentrations of MMP9, TIMP-1 and CRP were assessed by multiple regression analysis.
Results: Vitamin D status was the sole determinant of circulating MMP9 (inversely) and an independent determinant of CRP (inversely). Determinants of TIMP-1 were MMP9, systolic blood-pressure (directly) and VDR genotype (TaqI). Significant reductions in MMP9 (-68%), TIMP-1 (-38%) and CRP (-23%) concentrations followed vitamin-D supplementation.
Discussion: Vitamin-D insufficiency is associated with increased circulating MMP2,9 and CRP, correctable by supplementation. This finding provides a possible mechanism for tissue damage in chronic inflammatory conditions, including CHD and diabetes.
Address correspondence to Dr B.J. Boucher, Department of Diabetes and Metabolic Medicine, The Royal London Hospital, Whitechapel, London E1 BB. e-mail: bboucher{at}doctors.org.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. MASCITELLI, F. PEZZETTA, and M. R. GOLDSTEIN Menopause, vitamin D, and oral health (AUGUST 2009) Cleveland Clinic Journal of Medicine, November 1, 2009; 76(11): 629 - 629. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Tarcin, D. G. Yavuz, B. Ozben, A. Telli, A. V. Ogunc, M. Yuksel, A. Toprak, D. Yazici, S. Sancak, O. Deyneli, et al. Effect of Vitamin D Deficiency and Replacement on Endothelial Function in Asymptomatic Subjects J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 4023 - 4030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Reis, D. von Muhlen, E. R. Miller III, E. D. Michos, and L. J. Appel Vitamin D Status and Cardiometabolic Risk Factors in the United States Adolescent Population Pediatrics, September 1, 2009; 124(3): e371 - e379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Buell, T. M. Scott, B. Dawson-Hughes, G. E. Dallal, I. H. Rosenberg, M. F. Folstein, and K. L. Tucker Vitamin D Is Associated With Cognitive Function in Elders Receiving Home Health Services J Gerontol A Biol Sci Med Sci, August 1, 2009; 64A(8): 888 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Forouhi, J. Luan, A. Cooper, B. J. Boucher, and N. J. Wareham Baseline Serum 25-Hydroxy Vitamin D Is Predictive of Future Glycemic Status and Insulin Resistance: The Medical Research Council Ely Prospective Study 1990-2000 Diabetes, October 1, 2008; 57(10): 2619 - 2625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ritz Nephrology Potpourri Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1253 - 1259. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Alborzi, N. A. Patel, C. Peterson, J. E. Bills, D. M. Bekele, Z. Bunaye, R. P. Light, and R. Agarwal Paricalcitol Reduces Albuminuria and Inflammation in Chronic Kidney Disease: A Randomized Double-Blind Pilot Trial Hypertension, August 1, 2008; 52(2): 249 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Dobnig, S. Pilz, H. Scharnagl, W. Renner, U. Seelhorst, B. Wellnitz, J. Kinkeldei, B. O. Boehm, G. Weihrauch, and W. Maerz Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality Arch Intern Med, June 23, 2008; 168(12): 1340 - 1349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Giovannucci, Y. Liu, B. W. Hollis, and E. B. Rimm 25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men: A Prospective Study Arch Intern Med, June 9, 2008; 168(11): 1174 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Melamed, P. Muntner, E. D. Michos, J. Uribarri, C. Weber, J. Sharma, and P. Raggi Serum 25-Hydroxyvitamin D Levels and the Prevalence of Peripheral Arterial Disease: Results from NHANES 2001 to 2004 Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1179 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. McCann and B. N. Ames Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J, April 1, 2008; 22(4): 982 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Marino and N. Giotta Cinacalcet, fetuin-A and interleukin-6 Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1460 - 1461. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zittermann, S. S. Schleithoff, C. Gotting, O. Dronow, U. Fuchs, J. Kuhn, K. Kleesiek, G. Tenderich, and R. Koerfer Poor outcome in end-stage heart failure patients with low circulating calcitriol levels Eur J Heart Fail, March 1, 2008; 10(3): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M.-F. Yen, L.-S. Chen, Y.-H. Chiu, B. J Boucher, and T. H.-H. Chen A prospective community-population-registry based cohort study of the association between betel-quid chewing and cardiovascular disease in men in Taiwan (KCIS no. 19) Am. J. Clinical Nutrition, January 1, 2008; 87(1): 70 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Pittas, J. Lau, F. B. Hu, and B. Dawson-Hughes The Role of Vitamin D and Calcium in Type 2 Diabetes. A Systematic Review and Meta-Analysis J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2017 - 2029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Parekh, R. J. Chappell, A. E. Millen, D. M. Albert, and J. A. Mares Association Between Vitamin D and Age-Related Macular Degeneration in the Third National Health and Nutrition Examination Survey, 1988 Through 1994 Arch Ophthalmol, May 1, 2007; 125(5): 661 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Pittas, S. S. Harris, P. C. Stark, and B. Dawson-Hughes The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults Diabetes Care, April 1, 2007; 30(4): 980 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Michos and R. S. Blumenthal Vitamin D Supplementation and Cardiovascular Disease Risk Circulation, February 20, 2007; 115(7): 827 - 828. [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Harris Vitamin D and African Americans J. Nutr., April 1, 2006; 136(4): 1126 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cigolini, M. P. Iagulli, V. Miconi, M. Galiotto, S. Lombardi, and G. Targher Serum 25-hydroxyvitamin d3 concentrations and prevalence of cardiovascular disease among type 2 diabetic patients. Diabetes Care, March 1, 2006; 29(3): 722 - 724. [Full Text] [PDF]
|
|
|
|
|
|
W G. John, K. Noonan, N. Mannan, and B. J Boucher Hypovitaminosis D is associated with reductions in serum apolipoprotein A-I but not with fasting lipids in British Bangladeshis Am. J. Clinical Nutrition, September 1, 2005; 82(3): 517 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Teng, M. Wolf, M. N. Ofsthun, J. M. Lazarus, M. A. Hernan, C. A. Camargo Jr, and R. Thadhani Activated Injectable Vitamin D and Hemodialysis Survival: A Historical Cohort Study J. Am. Soc. Nephrol., April 1, 2005; 16(4): 1115 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J Boucher, W G. John, and K. Noonan Hypovitaminosis D is associated with insulin resistance and {beta} cell dysfunction Am. J. Clinical Nutrition, December 1, 2004; 80(6): 1666 - 1666. [Full Text] [PDF]
|
|
|
|
|
|
K. C Chiu Reply to BJ Boucher et al Am. J. Clinical Nutrition, December 1, 2004; 80(6): 1666 - 1667. [Full Text] [PDF]
|
|