The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males

被引:91
作者
Zitzmann, M
Brune, M
Kornmann, B
Gromoll, J
Junker, R
Nieschlag, E
机构
[1] Univ Munster, Inst Reprod Med, D-48129 Munster, Germany
[2] Univ Munster, Inst Clin Chem & Lab Med, D-48129 Munster, Germany
[3] Univ Munster, Inst Arteriosclerosis Res, D-48129 Munster, Germany
关键词
D O I
10.1046/j.1365-2265.2001.01391.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective Bone metabolism and bone density (BD) are influenced by sex hormones. Testosterone (T) action is exerted through the androgen receptor (AR). We investigated the potential impact of the CAG repeat (CAGR) polymorphism within the AR gene on BD and bone metabolism in healthy younger males. Patients and measurements The number of CAGRs in 110 healthy men aged 20-50 years was determined by sequence analysis. We assessed BD by the radiation-free method of quantitative ultrasound (QUS) of the phalanges. Serum levels of bone-specific alkaline phosphatase (BAP) and urine secretion of free deoxypyridinoline (DPD, corrected for creatinine), serum levels of sex hormones, body fat content and lifestyle factors were determined. Results In stepwise multiple regression models controlling for age, body fat content and lifestyle factors, the number of CAGRs was an independent negative predictor of BD (partial r = -0.286, P=0.001), whereas it was positively associated with markers of bone turnover (for BAP: partial r=0.32, P=0.001; for DPD: partial r=0.241, P=0.013). Levels of free T and oestradiol showed an independent and positive association with BD; age contributed significantly to lower BD. Age and free T were negatively associated with markers of bone turnover, whereas oestradiol showed a positive correlation with BAP and DPD. ANOVA in groups according to age and the CAGR length suggested an increased age-dependent bone loss in subjects with a CAGR length of 22-31 compared with 14-21 CAGRs (overall P<0.01). Conclusions A high number of CAG repeats within the androgen receptor gene attenuates testosterone effects on bone density and bone metabolism. This seems to be associated with accelerated age-dependent bone loss.
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页码:649 / 657
页数:9
相关论文
共 47 条
[1]   Estrogen receptor α gene polymorphisms and bone mineral density:: Haplotype analysis in women from the United Kingdom [J].
Albagha, OME ;
McGuigan, FEA ;
Reid, DM ;
Ralston, SH .
JOURNAL OF BONE AND MINERAL RESEARCH, 2001, 16 (01) :128-134
[2]   Ultrasound measurements at the proximal phalanges in healthy women and patients with hip fractures [J].
Alenfeld, FE ;
Wüster, C ;
Funck, C ;
Pereira-Lima, JFS ;
Fritz, T ;
Meeder, PJ ;
Ziegler, R .
OSTEOPOROSIS INTERNATIONAL, 1998, 8 (05) :393-398
[3]   Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor α gene and their relationship to bone mass variation in postmenopausal Italian women [J].
Becherini, L ;
Gennari, L ;
Masi, L ;
Mansani, R ;
Massart, F ;
Morelli, A ;
Falchetti, A ;
Gonnelli, S ;
Fiorelli, G ;
Tanini, A ;
Brandi, ML .
HUMAN MOLECULAR GENETICS, 2000, 9 (13) :2043-2050
[4]   Long-term effect of testosterone therapy on bone mineral density in hypogonadal men [J].
Behre, HM ;
Kliesch, S ;
Leifke, E ;
Link, TM ;
Nieschlag, E .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (08) :2386-2390
[5]   Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines [J].
Beilin, J ;
Ball, EMA ;
Favaloro, JM ;
Zajac, JD .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2000, 25 (01) :85-96
[6]   REGULATION OF INTERLEUKIN-6, OSTEOCLASTOGENESIS, AND BONE MASS BY ANDROGENS THE ROLE OF THE ANDROGEN RECEPTOR [J].
BELLIDO, T ;
JILKA, RL ;
BOYCE, BF ;
GIRASOLE, G ;
BROXMEYER, H ;
DALRYMPLE, SA ;
MURRAY, R ;
MANOLAGAS, SC .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (06) :2886-2895
[7]   ANALYSIS OF THE CAG REPEAT REGION OF THE ANDROGEN RECEPTOR GENE IN A KINDRED WITH X-LINKED SPINAL AND BULBAR MUSCULAR-ATROPHY [J].
BELSHAM, DD ;
YEE, WC ;
GREENBERG, CR ;
WROGEMANN, K .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1992, 112 (1-2) :133-138
[8]   Altered bone mineral density in patients with complete androgen insensitivity syndrome [J].
Bertelloni, S ;
Baroncelli, GI ;
Federico, G ;
Cappa, M ;
Lala, R ;
Saggese, G .
HORMONE RESEARCH, 1998, 50 (06) :309-314
[9]   THE LENGTH AND LOCATION OF CAG TRINUCLEOTIDE REPEATS IN THE ANDROGEN RECEPTOR N-TERMINAL DOMAIN AFFECT TRANSACTIVATION FUNCTION [J].
CHAMBERLAIN, NL ;
DRIVER, ED ;
MIESFELD, RL .
NUCLEIC ACIDS RESEARCH, 1994, 22 (15) :3181-3186
[10]   Mechanical strain stimulates osteoblast proliferation through the estrogen receptor in males as well as females [J].
Damien, E ;
Price, JS ;
Lanyon, LE .
JOURNAL OF BONE AND MINERAL RESEARCH, 2000, 15 (11) :2169-2177