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Effect of vitamin D receptor (VDR) genotypes on the risk for osteoporosis in type 1 Gaucher disease

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Abstract

The almost universal finding of osteopenia in Gaucher disease and the unpredictable advent of avascular necrosis and/or pathological fractures are clinically relevant issues that are not necessarily reversed by specific enzyme replacement therapy (ERT). However, genetic/epigenetic factors may explain variance for bone mineral density (BMD) in the normal population. Among the candidate genes, vitamin D receptor (VDR) polymorphisms have been correlated with BMD at the lumbar spine (LS) and femoral neck (FN) and/or fracture risk in various populations. Helsinki Committee approval was received. DNA samples from 15 healthy individuals and 83 non-neuronopathic adult patients with recent BMD data at LS and FN were tested for VDR polymorphisms FokI, ApaI, TaqI, and BsmI. Chi-square, Fisher’s exact, analysis of variance (ANOVA), Scheffe post hoc, and non-parametric Kruskal-Wallis ANOVA were applied as appropriate. P values <0.05 was considered statistically significant. There were no significant differences between patients and controls in frequency of any of polymorphic genotypes. The ApaI and BsmI genotypes were correlated with the N370S/N370S Gaucher genotype (p = 0.029, and p = 0.061, respectively). There was a correlation between the BsmI genotype and skeletal involvement (p = 0.018) and a trend to significance with Z scores at LS (p = 0.084). There was a statistically significant correlation between the Taq1 variants and BMD at the FN (p = 0.030) with the TT variant associated with lower BMD. As in other populations, VDR polymorphic genotype may be an independently sorting modifier in the prediction of BMD and bone involvement in Gaucher disease.

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References

  1. Beutler E, Grabowski GA (2001) Gaucher disease. In: Scriver CR, Valle D, Beudet A, Sly WS (eds) The metabolic and molecular bases of inherited diseases, vol III. McGraw-Hill, New York, pp 3635–3668

    Google Scholar 

  2. Elstein D, Itzchaki M, Mankin HJ (1997) Skeletal involvement in Gaucher disease. Clin Haematol 10:793–816

    CAS  Google Scholar 

  3. Pastores GM, Einhorn TA (1995) Skeletal complications of Gaucher disease: pathophysiology, evaluation and treatment. Semin Hematol 32:20–27

    Google Scholar 

  4. Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC, Mankin HJ, Murray GJ, Parker RI, Argoff CE et al (1991) Replacement therapy for inherited enzyme deficiency: macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med 324:1464–1470

    Article  CAS  PubMed  Google Scholar 

  5. Pastores GM, Wallenstein S, Desnick RJ, Luckey MM (1996) Bone density in type I Gaucher disease. J Bone Min Res 11:1801–1807

    Article  CAS  Google Scholar 

  6. Ciana G, Addobbati R, Tamaro G, Leopaldi A, Nevyjel M, Ronfani L, Vidoni L, Pittis MG, Bembi B (2005) Gaucher disease and bone: laboratory and skeletal mineral density variations during a long period of enzyme replacement therapy. J Inherit Metab Dis 28(5):723–732

    Article  CAS  PubMed  Google Scholar 

  7. Sims KB, Pastores GM, Weinreb NJ, Barranger J, Rosenbloom BE, Packman S, Kaplan P, Mankin H, Xavier R, Angell J, Fitzpatrick MA, Rosenthal D (2008) Improvement of bone disease by imiglucerase (Cerezyme) therapy in patients with skeletal manifestations of type 1 Gaucher disease: results of a 48-month longitudinal cohort study. Clin Genet 73(5):430–440

    Article  CAS  PubMed  Google Scholar 

  8. Parisi MS, Mastaglia SR, Bagur A, Goldstein G, Zeni SN, Oliveri B (2008) Body composition and bone metabolism in young Gaucher disease type I patients treated with imiglucerase. Eur J Med Res 13(1):31–38

    CAS  PubMed  Google Scholar 

  9. Koller DL, Econs MJ, Morin PA, Christian JC, Hui SL, Parry P, Curran ME, Rodriguez LA, Conneally PM, Joslyn G, Peacock M, Johnston CC, Foroud T (2000) Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis. J Clin Endocrinol Metab 85(9):3116–3120

    Article  CAS  PubMed  Google Scholar 

  10. Ferrari SL, Rizzoli R (2005) Gene variants for osteoporosis and their pleiotropic effects in aging. Mol Aspects Med 26(3):145–167

    Article  CAS  PubMed  Google Scholar 

  11. Valdivielso JM, Fernandez E (2006) Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 371:1–12

    Article  CAS  PubMed  Google Scholar 

  12. Alvarez-Hernandez D, Naves-Diaz M, Gomez-Alonso C, Coto E, Cannata-Andia JB (2008) Tissue-specific effect of VDR gene polymorphisms on the response to calcitriol. J Nephrol 21(6):843–849

    CAS  PubMed  Google Scholar 

  13. Thakkinstian A, D'Este C, Eisman J, Nguyen T, Attia J (2004) Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study. J Bone Miner Res 19(3):419–428

    Article  CAS  PubMed  Google Scholar 

  14. Dundar U, Solak M, Kavuncu V, Ozdemir M, Cakir T, Yildiz H, Evcik D (2009) Evidence of association of Vitamin D receptor Apa I gene polymorphism with bone mineral density in postmenopausal women with osteoporosis. Clin Rheumatol 28(10):1187–1191

    Article  PubMed  Google Scholar 

  15. Horst-Sikorska W, Kalak R, Wawrzyniak A, Marcinkowska M, Celczynska-Bajew L, Slomski R (2007) Association analysis of the polymorphisms of the VDR gene with bone mineral density and the occurrence of fractures. J Bone Miner Metab 25(5):310–319

    Article  CAS  PubMed  Google Scholar 

  16. Remes T, Vaisanen SB, Mahonen A, Huuskonen J, Kroger H, Jurvelin JS, Rauramaa R (2005) Bone mineral density, body height, and vitamin D receptor gene polymorphism in middle-aged men. Ann Med 37(5):383–392

    Article  CAS  PubMed  Google Scholar 

  17. Mencej-Bedrac S, Prezelj J, Kocjan T, Teskac K, Ostanek B, Smelcer M, Marc J (2009) The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density. J Mol Endocrinol 42(3):239–247

    Article  CAS  PubMed  Google Scholar 

  18. Arnheim E, Chicco G, Phillips M, Lebel E, Foldes AJ, Itzchaki M, Elstein D, Zimran A, Altarescu G (2008) Molecular aspects of osteopathy in type 1 Gaucher disease: correlation between genetics and bone density. Rheumatol Int 28(9):873–877

    Article  PubMed  Google Scholar 

  19. Grundberg E, Lau EM, Pastinen T, Kindmark A, Nilsson O, Ljunggren O, Mellström D, Orwoll E, Redlund-Johnell I, Holmberg A, Gurd S, Leung PC, Kwok T, Ohlsson C, Mallmin H, Brändström H (2007) Vitamin D receptor 3′ haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong. J Bone Miner Res 22(6):832–840

    Article  CAS  PubMed  Google Scholar 

  20. Zimran A, Sorge J, Gross E, Kubitz M, West C, Beutler E (1989) Prediction of severity of Gaucher's disease by identification of mutations at DNA level. Lancet 2:349–352

    Article  CAS  PubMed  Google Scholar 

  21. Cooper C, Harvey N, Javaid K, Hanson M, Dennison E (2008) Growth and bone development. Nestle Nutr Workshop Ser Pediatr Program 61:53–68

    Article  PubMed  Google Scholar 

  22. Eckstein M, Vered I, Ish-Shalom S, Shlomo AB, Shtriker A, Koren-Morag N, Friedman E (2002) Vitamin D and calcium-sensing receptor genotypes in men and premenopausal women with low bone mineral density. Isr Med Assoc J 4(5):340–344

    CAS  PubMed  Google Scholar 

  23. Dresner-Pollak R, Ackerman Z, Eliakim R, Karban A, Chowers Y, Fidder HH (2004) The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients. Genet Test 8(4):417–420

    Article  CAS  PubMed  Google Scholar 

  24. Uitterlinden AG, Ralston SH, Brandi ML, Carey AH, Grinberg D, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Reeve J, Reid DM, Amedei A, Bassiti A, Bustamante M, Husted LB, Diez-Perez A, Dobnig H, Dunning AM, Enjuanes A, Fahrleitner-Pammer A, Fang Y, Karczmarewicz E, Kruk M, van Leeuwen JP, Mavilia C, van Meurs JB, Mangion J, McGuigan FE, Pols HA, Renner W, Rivadeneira F, van Schoor NM, Scollen S, Sherlock RE, Ioannidis JP, APOSS Investigators; EPOS Investigators; EPOLOS Investigators; FAMOS Investigators; LASA Investigators; Rotterdam Study Investigators; GENOMOS Study (2006) The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann Intern Med 145(4):255–264

    CAS  PubMed  Google Scholar 

  25. Langdahl BL, Gravholt CH, Brixen K, Eriksen EF (2000) Polymorphisms in the vitamin D receptor gene and bone mass, bone turnover and osteoporotic fractures. Eur J Clin Invest 30:608–617

    Article  CAS  PubMed  Google Scholar 

  26. Riggs BL, Nguyen TV, Melton LJ 3rd, Morrison NA, O'Fallon WM, Kelly PJ, Egan KS, Sambrook PN, Muhs JM, Eisman JA (1995) The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women. J Bone Miner Res 10(6):991–996

    Article  CAS  PubMed  Google Scholar 

  27. Mitra S, Desai M, Ikram Khatkhatay M (2006) Vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal Indian women. Maturitas 55(1):27–35

    Article  CAS  PubMed  Google Scholar 

  28. Remes T, Väisänen SB, Mahonen A, Huuskonen J, Kröger H, Jurvelin JS, Rauramaa R (2005) Bone mineral density, body height, and vitamin D receptor gene polymorphism in middle-aged men. Ann Med 37:383–392

    Article  CAS  PubMed  Google Scholar 

  29. Nguyen TV, Esteban LM, White CP, Grant SF, Center JR, Gardiner EM, Eisman JA (2005) Contribution of the collagen I alpha1 and vitamin D receptor genes to the risk of hip fracture in elderly women. J Clin Endocrinol Metab 90:6575–6579

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Gaucher Clinic, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem, 91031, Israel

    Allen Greenwood, Deborah Elstein & Ari Zimran

  2. Genetics Unit, Shaare Zedek Medical Center, Jerusalem, Israel

    Gheona Altarescu

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  1. Allen Greenwood
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  2. Deborah Elstein
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  3. Ari Zimran
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  4. Gheona Altarescu
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Correspondence to Deborah Elstein.

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Greenwood, A., Elstein, D., Zimran, A. et al. Effect of vitamin D receptor (VDR) genotypes on the risk for osteoporosis in type 1 Gaucher disease. Clin Rheumatol 29, 1037–1041 (2010). https://doi.org/10.1007/s10067-010-1464-9

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  • DOI: https://doi.org/10.1007/s10067-010-1464-9

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