A CAG repeat polymorphism in the androgen receptor gene is associated with reduced bone mass and increased risk of osteoporotic fractures

Calcified Tissue International

Volumn 73, Issue 3, 2003, Pages 237-243

  Langdahl, B L ^a   Stenkjaer L ^a   Carstens, M ^a   Tofteng, C L ^b   Eriksen, E F ^a  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

^b HVIDOVRE HOSPITAL   (Denmark)

Author keywords

Androgen receptor; Bone mass; Bone turnover; Osteoporosis; Polymorphism

Indexed keywords

ADENINE; ANDROGEN RECEPTOR; BIOCHEMICAL MARKER; CYTOSINE; ESTROGEN RECEPTOR; GUANINE;

ADULT; AGED; ALLELE; ARTICLE; BONE DENSITY; BONE MASS; BONE MINERAL; BONE TURNOVER; CONTROLLED STUDY; CORRELATION ANALYSIS; DNA POLYMORPHISM; DUAL ENERGY X RAY ABSORPTIOMETRY; EXON; FEMALE; FEMUR NECK; FRAGILITY FRACTURE; GENE FREQUENCY; GENE FUNCTION; GENE STRUCTURE; HIP; HUMAN; HYPOGONADISM; LINEAR REGRESSION ANALYSIS; LOGISTIC REGRESSION ANALYSIS; LUMBAR SPINE; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE REPEAT; OSTEOPOROSIS; PREDICTION; PRIORITY JOURNAL; RISK ASSESSMENT; SCORING SYSTEM; SEQUENCE ANALYSIS; SEX DIFFERENCE; TRANSCRIPTION REGULATION; VERTEBRA FRACTURE;

ADULT; AGED; AGED, 80 AND OVER; ALLELES; BIOLOGICAL MARKERS; BONE DENSITY; BONE REMODELING; CASE-CONTROL STUDIES; DENSITOMETRY, X-RAY; DNA; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; MIDDLE AGED; OSTEOPOROSIS; POLYMERASE CHAIN REACTION; POLYMORPHISM, GENETIC; RECEPTORS, ANDROGEN; RISK FACTORS; SPINAL DISEASES; SPINAL FRACTURES; TRINUCLEOTIDE REPEATS;

EID: 0141857853     PISSN: 0171967X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00223-002-0019-8     Document Type: Article

References (51)

1. Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberi S (1987) Genetic determinants of bone mass in adults. A twin study. J Clin Invest 80:706-710
2. Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC (1991) Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 6:561-567
3. Soroko SB, Barrett-Connor E, Edelstein SL, Kritz-Silverstein D (1994) Family history of osteoporosis and bone mineral density at the axial skeleton: the Rancho Bernardo Study. J Bone Miner Res 9:761-769
4. Gueguen R, Jouanny P, Guillemin F, Kuntz C, Pourel J, Siest G (1995) Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 10:2017-2022
5. Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516-1517
6. Langdahl BL, Lokke E, Carstens M, Stenkjaer LL, Eriksen EF (2000) A TA repeat polymorphism in the estrogen receptor gene is associated with osteoporotic fractures but polymorphisms in the first exon and intron are not. J Bone Miner Res 15:2222-2230
7. Albagha OM, McGuigan FE, Reid DM, Ralston SH (2001) Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom. J Bone Miner Res 16:128-134
8. Ongphiphadhanakul B, Rajatanavin R, Chanprasertyothin S, Piaseu N, Chailurkit L, Sirisriro R, Komindr S (1998) Estrogen receptor gene polymorphism is associated with bone mineral density in premenopausal women but not in postmenopausal women. J Endocrinol Invest 21:487-493
9. Edwards A, Hammond HA, Jin L, Caskey CT, Chakraborty R (1992) Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics 12:241-253
10. Chamberlain NL, Driver ED, Miesfeld RL (1994) The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 22:3181-3186
11. Kazemi-Esfarjani P, Trifiro MA, Pinsky L (1995) Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG)n-expanded neuronopathies. Hum Mol Genet 4:523-527
12. Tut TG, Ghadessy FJ, Trifiro MA, Pinsky L, Yong EL (1997) Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J Clin Endocrinol Metab 82:3777-3782
13. Mhatre AN, Trifiro MA, Kaufman M, Kazemi-Esfarjani D, Figlewicz D, Rouleau G, Pinsky L (1993) Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nat Genet 5:184-188
14. Irvine RA, Yu MC, Ross RK, Coetzee GA (1995) The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. Cancer Res 55:1937-1940
15. Wallerand H, Remy-Martin A, Chabannes E, Bermont L, Adessi G, Bittard H (2001) Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility. Fertil Steril 76:769-774
16. Dowsing AT, Yong EL, Clark M, McLachlan RI, de Kretser DM, Trounson AO (1999) Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene [see comments]. Lancet 354:640-643
17. Mitsumori K, Terai A, Oka H, Segawa T, Ogura K, Yoshida O, Ogawa O (1999) Androgen receptor CAG repeat length polymorphism in benign prostatic hyperplasia (BPH): correlation with adenoma growth. Prostate 41:253-257
18. Modugno F, Weissfeld JL, Trump DL, Zmuda JM, Shea JA, Cauley JA, Ferrell RE (2001) Allelic variants of aromatase and the androgen and estrogen receptors: toward a multigenic model of prostate cancer risk. Clin Cancer Res 7:3092-3096
19. Hardy DO, Scher HI, Bogenreider T, Sabbatini P, Zhang DM, Nanus DM, Catterall JF (1996) Androgen receptor CAG repeat lengths in prostate cancer: correlation with age of onset. J Clin Endocrinol Metab 81:4400-4405
20. Beilin J, Harewood L, Frydenberg M, Mameghan H, Martyres RF, Farish SJ, Yue C, Deam DR, Byron KA, Zajac JD (2001) A case-control study of the androgen receptor gene CAG repeat polymorphism in Australian prostate carcinoma subjects. Cancer 92:941-949
21. Giovannucci E, Stampfer MJ, Krithivas K, Brown M, Dahl D, Brufsky A, Talcott J, Hennekens CH, Kantoff PW (1997) The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci USA 94:3320-3323
22. Giwercman YL, Xu C, Arver S, Pousette A, Reneland R (1998) No association between the androgen receptor gene CAG repeat and impaired sperm production in Swedish men. Clin Genet 54:435-436
23. Miller EA, Stanford JL, Hsu L, Noonan E, Ostrander EA (2001) Polymorphic repeats in the androgen receptor gene in high-risk sibships. Prostate 48:200-205
24. Bousema JT, Bussemakers MJ, van Houwelingen KP, Debruyne FM, Verbeek AL, de La Rosette JJ, Kiemeney LA (2000) Polymorphisms in the vitamin D receptor gene and the androgen receptor gene and the risk of benign prostatic hyperplasia. Eur Urol 37:234-238
25. Lange EM, Chen H, Brierley K, Livermore H, Wojno KJ, Langefeld CD, Lange K, Cooney KA (2000) The polymorphic exon 1 androgen receptor CAG repeat in men with a potential inherited predisposition to prostate cancer. Cancer Epidemiol Biomarkers Prev 9:439-442
26. Edwards SM, Badzioch MD, Minter R et al. (1999) Androgen receptor polymorphisms: association with prostate cancer risk, relapse and overall survival. Int J Cancer 84:458-465
27. Latil AG, Azzouzi R, Cancel GS, Guillaume EC, Cochan-Priollet B, Berthon PL, Cussenot O (2001) Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways. Cancer 92:1130-1137
28. Yaron M, Levy T, Chetrit A, Levavi H, Sabah G, Schneider D, Halperin R, Ben Rafael Z, Friedman E (2001) The polymorphic CAG repeat in the androgen receptor gene in Jewish Israeli women with endometrial carcinoma. Cancer 92:1190-1194
29. Levine DA, Boyd J (2001) The androgen receptor and genetic susceptibility to ovarian cancer: results from a case series. Cancer Res 61:908-911
30. Giguere Y, Dewailly E, Brisson J, Ayotte P, Laflamme N, Demers A, Forest VI, Dodin S, Robert J, Rousseau F (2001) Short polyglutamine tracts in the androgen receptor are protective against breast cancer in the general population. Cancer Res 61:5869-5874
31. Yu H, Bharaj B, Vassilikos EJ, Giai M, Diamandis EP (2000) Shorter CAG repeat length in the androgen receptor gene is associated with more aggressive forms of breast cancer. Breast Cancer Res Treat 59:153-161
32. Legro RS, Shahbahrami B, Lobo RA, Kovacs BW (1994) Size polymorphisms of the androgen receptor among female Hispanics and correlation with androgenic characteristics. Obstet Gynecol 83:701-706
33. Sowers M, Willing M, Burns T, Deschenes S, Hollis B, Crutchfield M, Jannausch M (1999) Genetic markers, bone mineral density, and serum osteocalcin levels. J Bone Miner Res 14:1411-1419
34. Zitzmann M, Brune M, Kornmann B, Gromoll J, Junker E, Nieschlag E (2001) The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males. Clin Endocrinol (Oxf) 55:649-657
35. van Pottelbergh I, Lumbroso S, Goemaere S, Sultan C, Kaufman JM (2001) Lack of influence of the androgen receptor gene CAG-repeat polymorphism on sex steroid status and bone metabolism in elderly men. Clin Endocrinol (Oxf) 55:659-666
36. Salmen T, Heikkinen AM, Mahonen A, Kroger H, Komulainen M, Pallonen H, Saarikoski S, Honkanen R, Maenpaa PH (2003) Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial. J Bone Miner Res 18:319-324
37. Dunning AM, McBride S, Gregory J, Durocher F, Foster CS, Healey CS, Smith N, Pharoah PD, Luben RN, Easton BA, Ponder BA (1999) No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer. Carcinogenesis 20:2131-2135
38. Genant HK, Grampp S, Gluer CC, Faulkner KG, Jergas K, Engelke K, Hagiwara S, Van Kuijk C (1994) Universal standardization for dual x-ray absorptiometry: patient and phantom cross-calibration results [see comments]. J Bone Miner Res 9:1503-1514
39. Risteli J, Elomaa I, Niemi S, Novamo A, Risteli L (1993) Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem 39:635-640
40. Nielsen HK, Laurberg P, Brixen K, Mosekilde L (1991) Relations between diurnal variations in serum osteocalcin, cortisol, parathyroid hormone, and ionized calcium in normal individuals. Acta Endocrinol (Copenh) 124:391-398
41. Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones Jr HW, Rary JM (1977) Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 74:1245-1249
42. Mori K, Ushiyama T, Inoue K, Hukuda S (2000) Polymorphic CAG repeats of the androgen receptor gene in Japanese male patients with ankylosing spondylitis. Rheumatology (Oxford) 39:530-532
43. Tanner SM, Orstavik KH, Kristiansen M, Lev D, Lerman-Sagie T, Sadeh M, Liechti-Gallati S (1999) Skewed X-inactivation in a manifesting carrier of X-linked myotubular myopathy and in her non-manifesting carrier mother. Hum Genet 104:249-253
44. Naumova AK, Olien L, Bird LM, Smith M, Verner AE, Leppert M, Morgan K, Sapienza C (1998) Genetic mapping of X-linked loci involved in skewing of X chromosome inactivation in the human. Eur J Hum Genet 6:552-562
45. Naumova AK, Plenge RM, Bird LM, Leppert M, Morgan HF, Willard HF, Sapienza C (1996) Heritability of X chromosome-inactivation phenotype in a large family. Am J Hum Genet 58:1111-1119
46. Calvo RM, Asuncion M, Sancho J, San Millan JL, Escobar-Morreale HF (2000) The role of the CAG repeat polymorphism in the androgen receptor gene and of skewed X-chromosome inactivation, in the pathogenesis of hirsutism. J Clin Endocrinol Metab 85:1735-1740
47. Westberg L, Baghaei F, Rosmond R, Hellstrand M, Landen M, Jansson M, Holm G, Bjomtorp P, Eriksson E (2001) Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women. J Clin Endocrinol Metab 86:2562-2568
48. Vanderschueren D, van Herck E, De Coster R, Bouillon R (1996) Aromatization of androgens is important for skeletal maintenance of aged male rats. Calcif tissue Int 59:179-183
49. Vanderschueren D, van Herck E, Nijs J, Ederveen AG, De Coster R, Bouillon R (1997) Aromatase inhibition impairs skeletal modeling and decreases bone mineral density in growing male rats. Endocrinology 138:2301-2307
50. Krithivas K, Yurgalevitch SM, Mohr BA, Wilcox CJ, Batter SJ, Brown M, Longcope C, McKinlay JB, Kantoff PW (1999) Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men. J Endocrinol 162:137-142
51. Kawasaki T, Ushiyama T, Ueyama H, Inoue K, Mori K, Ohkubo I, Hukuda S (1999) Polymorphic CAG repeats of the androgen receptor gene and rheumatoid arthritis. Ann Rheum Dis 58:500-502