Summary
It has been suggested that inherited traits play a role in the development of osteoporosis by providing a background for the modulation of gene expression. In this study, we examine the influence of the different alleles of alpha2-HS glycoprotein (AHSG), a protein of the bone matrix, on quantitative estrogens, estrone and estradiol, and bone measures, bone area and density. Estrogens provide a protective effect against fractures in older women and were thus included in the analyses. Isoelectric focusing of AHSG from sera followed by immunoblotting was used to type 163 white post-menopausal women participating in a clinical trial of the effects of walking on bone loss. Plasma hormones were measured by a combination of extraction, column chromatography, and radioimmunoassay; bone measures on the dominant radius were determined with computerized tomography. Analysis of variance was done on estrogen and bone measures after controlling for the effects of age and body mass index. The two major alleles of AHSG result in three phenotypes, designated AHSG 1-1, AHSG 2-1, and AHSG 2-2. The AHSG 1-1 homozygote showed a decreased concentration of estradiol, the AHSG 2-2 homozygote showed an increased concentration, and the AHSG 2-1 heterozygote was intermediate (P=0.001). Estrone demonstrated a similar pattern in residual analysis although it did not reach statistical significance.
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Smith DM, Nance WE, Kang KW, Christian JC, Johnston CC Jr (1973) Genetic factors in determining bone mass. J Clin Invest 52:2800–2808
Riggs BL, Melton LJ III (1986) Involutional osteoporosis. N Engl J Med 314:1676–1686
Dickson IR, Bagga MK (1985) Changes with age in the non-collagenous proteins of human bone. Connect Tissue Res 14:77–85
Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, Riggs BL (1988) Evidence of estrogen receptors in normal human osteoblast-like cells. Science 241:84–86
Lindsay R, Hart DM, Forrest C, Baird C (1980) Prevention of spinal osteoporosis in oophorectomized women. Lancet ii:1151–1153
Kiel DP, Felson DT, Anderson JJ, Wilson PW, Moskowitz MA (1987) Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study. N Engl J Med 317:1169–1174
Cauley JA, Gutai JP, Sandler RB, LaPorte RE, Kuller LH, Sashin D (1986) The relationship of endogenous estrogen to bone density and bone area in normal postmenopausal women. Am J Epidemiol 124:752–761
Putnam FW (1984) Progress in plasma proteins. In: Putnam FW (ed) The plasma proteins, vol 4 Academic Press, New York, pp 1–44
Heremans JF (1960) Les globulines sériques du système gamma. In: Heremans JF (ed) Arscia, Brussels, pp 103–105
Schmid K, Bürgi W (1961) Preparation and properties of the human plasma Ba-α2-glycoproteins. Biochim Biophys Acta 47:440–453
Van Oss CJ, Gillman CF, Bronson PM, Border JR (1974) Opsonic properties of human serum alpha-2 HS glycoprotein. Immunol Commun 3:329–335
Lebreton JP, Joisel F, Raoult JP, Lannuzel B, Rogez JP, Humbert G (1979) Serum concentration of human alpha2HS glycoprotein during the inflammatory process. J Clin Invest 64:1118–1129
Triffit JT (1980) Organic matrix of bone tissue. In: Urist MR (ed) Fundamental and clinical bone physiology. JB Lippincott, New York, pp 45–82
Dickson IR, Poole AR, Veis A (1975) Localisation of plasma α2HS glycoprotein in mineralising human bone. Nature 256:430–432
Ashton BA, Höhling H-J, Triffit JT (1976) Plasma proteins present in human cortical bone: enrichment of the α2H-S glycoprotein. Calcif Tissue Res 22:27–23
Triffit JT, Gebauer U, Ashton BA, Owen ME, Reynolds JJ (1976) Origin of plasma α2HS-glycoprotein and its accumulation in bone. Nature 262:226–227
Malone JD, Teitelbaum SL, Griffin GL, Senior RM, Kahn AJ (1982) Recruitment of osteoclast precursors by purified bone matrix constituents. J Cell Biol 92:227–230
Anderson NL, Anderson NG (1977) High resolution two-dimensional electrophoresis of human plasma proteins. Proc Natl Acad Sci USA 74:5421–5425
Umetsu K, Kashimura S, Ikeda N, Suzuki T (1984) A new α2HS-glycoprotein allele (AHS*5) in two Japanese families. Hum Genet 68:264–265
Boutin B, Ferg SH, Arnaud P (1985) The genetic polymorphism of alpha2HS glycoprotein: study by ultrathin-layer isoelectric focusing and immunoblot. Am J Hum Genet 37:1098–1105
Cox DW, Andrews BJ, Wills DE (1986) Genetic polymorphism of α2HS glycoprotein. Am J Hum Genet 38:699–706
Korenman SG, Stevens RH, Carpenter LA, Robb M, Niswender GD, Sherman BM (1974) Estradiol radioimmunoassay without chromatography: procedure, validation and normal values. J Clin Endocrinol Metab 38:718–720
Radfar N, Ansusingha K, Kenny FM (1976) Circulating bound and free estradiol and estrone during normal growth and development and in premature thelarche and isosexual precocity. J Pediatr 89:719–723
Sherman BM (1987) Endocrinologic and menstrual alterations. In: Mishell DR (ed) Menopause: physiology and pharmacology. Year Book Medical Publishers, Chicago, pp 41–51
Sashin D, Sternglass EJ, Sandler RB, Slasky BS, Herbert DL, LaPorte RE, Cauley J, Pollitt AE (1983) The development and evaluation of a CT technique for measurement of the density of cortical bones in the appendicular skeleton. J Comput Assists Tomogr 7:552
Schlenker RA (1976) Percentages of cortical and trabecular bone mineral mass in the radius and ulna. Am J Roentgenol 126:1309–1312
Sandler RB, LaPorte RE, Sashin D, Kuller LH, Sternglass E, Cauley JA, Link MM (1982) Determinants of bone mass in menopause. Prev Med 11:269–280
Weidinger S, Schwarzfischer F, Burgemeister R, Cleve H (1984) Genetic alpha-2-HS glycoprotein phenotypes demonstrated by isoelectric focusing and immunofixation. In: Neuhoff V (ed) Electrophoresis 1984. Verlag Chemie, Weinheim, pp 487–490
Heaney RP (1982) Paradox of irreversibility of age-related bone loss. In: Menczel J, Robin GC, Makin M, Steinberg R (eds) Osteoporosis. Proceedings of International Symposium held at the Jerusalem Osteoporosis Center in June 1981, John Wiley, New York, pp 15–20
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Eichner, J.E., Friedrich, C.A., Cauley, J.A. et al. Alpha2-HS glycoprotein phenotypes and quantitative hormone and bone measures in postmenopausal women. Calcif Tissue Int 47, 345–349 (1990). https://doi.org/10.1007/BF02555885
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DOI: https://doi.org/10.1007/BF02555885