Abstract
Osteoporosis is a slowly progressing disease resulting from an imbalance between bone accretion and degradation. As interstitial collagenase is a key enzyme in the degradatior of bone matrix, we investigated a possible relationship between the collagenase gene and osteoporosis. Analysis of an amplified genomic DNA fragment from-524 to +52 by denaturing gradient gel electrophoresis and sequencing allowed us to detect three dimorphic sites upstream of base-300, one of them leading to a BanI restriction site. None of the sites could be directly associated with osteoporosis. The allele frequencies of the three dimorphic sites were estimated. The interallelic ratios were high, thus providing new useful genetic markers for linkage analysis. When comparing these ratios in osteoporotic and nonosteoporotic subjects, no significant differences could be observed.
Similar content being viewed by others
References
Pocock NA, Eisman JA, Hopper J, Yeates M, Sambrook PN, Eberl S (1987) Genetic determinants of bone mass in adults. J. Clin Invest 80:706–710
Dequeker J, Nijs J, Verstaeten A, Geusen P, Gevers G (1987) Genetic determinants of bone mineral content at the spine and radius: a twin study. Bone 8:207–209
Seeman E, Hopper JL, Bach LA, Cooper ME, Parkinson E, McKay J, Jerums G (1989) Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 320:554–558
Kelly PJ, Hopper JL, Macaskill GT, Pocock NA, Sambrook PN, Eisman JA (1991) Genetic factors in bone turnover. J Clin Endocrinol Metab 72:808–813
Shapiro JR, Burn VE, Chipman SD, Velis KP, Bansal M (1989) Osteoporosis and familial idiopathic scoliosis: association with an abnormal alpha 2(1) collagen. Connect Tissue Res 21:117–124
Spotila LD, Constantinou CD, Sereda L, Ganguly A, Riggs BL, Prockop DJ (1991) Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta. Proc Natl Acad Sci USA 8:5423–5427
Nicholls AC, Oliver J, Renouf DV, Heath DA, Pope FM (1992) The molecular defect in a family with mild atypical osteogenesis imperfecta and extreme joint hypermobility: exon skipping caused by an 11-bp deletion from an intron in one COL1A2 allele. Hum Genet 88:627–633
Baylink DJ, Finkelmen RD, Mohan S (1993) Growth factors to stimulate bone formation. J Bone Miner Res 8:S565-S572
Canalis E, McCarthy TL, Centrella M (1989) The role of growth factors in skeletal remodeling. Endocrinol Metab Clin North Am 18:903–918
Morrison NA, Cheng Qi J, Tonkita A, Kelly PJ, Crofts L, Ngugen TV, Sambrook PN, Eisman JA (1994) Prediction of bone density from vitamin D receptor alleles. Lett Nature 367:284–287
Angel P, Baumann I, Stein B, Delius H, Rahmsdorf H, Herrlich P (1987) 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region. Mol Cell Biol 7:2256–2266
Mauviel A, Chen YQ, Dong W, Evans CH, Uitto J (1993) Transcriptional interactions of transforming growth-factor-β with pro-inflammatory cytokines. Curr Biol 3:822–831
Reginster JY, Denis D, Deroisy R, Albert A, Sarlet N, Collette J, Franchimont P (1990) Dual photon absorptiometry of lumbar spine in West European (Belgian) postmenopausal females: normal range and fracture threshold. Clin Rheumat 9:220–224
Kawasaki ES (1990) Sample preparation from blood, cells, and other fluids. In: Innis MA, Gelfland DH, Sninsky JJ, White TJ (eds) PCR protocols: a guide to methods and applications. Academic Press, San Diego, pp 146–152
Myers RM, Sheffield VC, Cox DR (1988) Detection of single base changes in DNA: ribonuclease cleavage and denaturing gradient gel electrophoresis. In: Davies KE (ed) Genome analysis: a practical approach. IRL Press, Oxford, pp 95–139
Winship PR (1989) An improved method for directly sequencing PCR amplified material using dimethyl sulphoxide. Nucl Acid Res 17:1266
Delaissé JM, Vaes G (1992) Mechanism of mineral solubilization and matrix degradation in osteoclastic bone resorption. In: Rifkin BR, Gay CV (eds) Biology and physiology of the osteoclast. CRC Press, Boca Raton, pp 290–314
Cato ACB, König H, Ponta H, Herrlich P (1992) Steroïds and growth-promoting factors in the regulation of expression of genes and gene networks. J Steroïd Biochem Molec Biol 43:63–68
Johnson RS, Spiegelman BM, Papaioannou V (1992) Pleiotropic effects of a null mutation in the c-fos Proto-oncogene. Cell 71: 577–586
Manca L, Cocco E, Gallisai D, Masala B, Gilman GJ (1991) Diminished AgammaT fetal globin levels in Sardinian haplotype II 91-1 thalassaemia patients are associated with a four base pair deletion in the AgammaT promoter, Br J Haematol 78:105–107
Beldjord C, Ducrocq R, Nadifi S, Lapoumeroulie C, Elion J, Labie D (1992) A haplotype-linked four base pair deletion upstream of the Agamma globin gene coincides with decreased expression. Hum Genet 89:625–628
Prockop DJ (1992) Mutations in collagen genes as a cause of connective-tissue diseases. N Engl J Med 326:540–546
Colombi M, Gardella R, Zoppi N, Moro L, Marini D, Spurr NK, Barlati S (1992) Exclusion of stromelysin-1, stromelysin-2, interstitial collagenase and fibronectin genes as the mutant loci in a family with recessive epidermolysis bullosa dystrophica and a form of cerebellar ataxia. Hum Genet 89:503–507
Hovnanian A, Duquesnoy P, Amselem S, Blanchet-Bardon C, Lathrop M, Dubertret L, Goossens M (1991) Exclusions of linkage between the collagenase gene and generalized recessive dystrophic epidermolysis bullosa phenotype. J Clin Invest 88:1716–1721
Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M (1987) Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 49:729–739
Gutman A, Wasylyk B (1990) The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites. EMBO J 9:2241–2246
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Thiry-Blaise, L.M., Taquet, A.N., Reginster, J.Y. et al. Investigation of the relationship between osteoporosis and the collagenase gene by means of polymorphism of the 5′upstream region of this gene. Calcif Tissue Int 56, 88–91 (1995). https://doi.org/10.1007/BF00298750
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00298750