Zitzmann M, Brune M, Kornmann B, Gromoll J, Junker R, Nieschlag E
Institute of Reproductive Medicine of the University, Münster, Germany.
Clin Endocrinol (Oxf). 2001 Nov;55(5):649-57. doi: 10.1046/j.1365-2265.2001.01391.x.
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.
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.
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).
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.
骨代谢和骨密度（BD）受性激素影响。睾酮（T）通过雄激素受体（AR）发挥作用。我们研究了AR基因内CAG重复序列（CAGR）多态性对健康年轻男性骨密度和骨代谢的潜在影响。
通过序列分析确定了110名年龄在20 - 50岁的健康男性的CAGRs数量。我们采用无辐射的指骨定量超声（QUS）方法评估骨密度。测定了血清骨特异性碱性磷酸酶（BAP）水平、尿游离脱氧吡啶啉（DPD，校正肌酐后）分泌量、性激素血清水平、体脂含量和生活方式因素。
在控制年龄、体脂含量和生活方式因素的逐步多元回归模型中，CAGRs数量是骨密度的独立负向预测因子（偏相关系数r = - 0.286，P = 0.001），而它与骨转换标志物呈正相关（对于BAP：偏相关系数r = 0.32，P = 0.001；对于DPD：偏相关系数r = 0.241，P = 0.013）。游离T和雌二醇水平与骨密度呈独立正相关；年龄对骨密度降低有显著影响。年龄和游离T与骨转换标志物呈负相关，而雌二醇与BAP和DPD呈正相关。根据年龄和CAGR长度分组的方差分析表明，与CAGR长度为14 - 21的受试者相比，CAGR长度为22 - 31的受试者年龄依赖性骨丢失增加（总体P < 0.01）。
雄激素受体基因内大量的CAG重复序列减弱了睾酮对骨密度和骨代谢的作用。这似乎与年龄依赖性骨丢失加速有关。
