Langdahl B L, Stenkjaer L, Carstens M, Tofteng C L, Eriksen E F
Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Amtssygehus, DK-8000 Aarhus, Denmark.
Calcif Tissue Int. 2003 Sep;73(3):237-43. doi: 10.1007/s00223-002-0019-8.
Osteoporosis is a common disease with a strong genetic component. Hypogonadism results in low bone mass and it increases significantly the risk of osteoporosis in both sexes. The estrogen and androgen receptor genes are therefore strong candidates for mediating the genetic influence on bone mass and risk of osteoporosis. A CAG repeat in the first exon of the androgen receptor (AR) is associated with reduced transcriptional activity of the AR. We therefore examined whether this CAG repeat polymorphism is associated with changes in bone mass and risk of osteoporotic fractures in 284 osteoporotic patients with vertebral fractures and 327 normal individuals. The number of CAG repeats varied between 13 and 30 in men and between 7 and 34 in women. The short and long alleles comprised 19.2 +/- 2.5 and 19.0 +/- 2.3 repeats (ns) and 22.7 +/- 2.4 and 21.9 +/- 2.4 (P < 0.01) in women with vertebral fractures and normal women, respectively. This difference was also reflected in the average number of CAG repeats: 21.0 +/- 2.0 in osteoporotic women vs. 20.5 +/- 2.0 in normal women (P < 0.05). 54.8% of women with osteoporotic fractures vs. 45.9% of normal women had average number of CAG repeats of 21 and more (chi2 = 3.11, P = 0.08). Logistic regression analyses revealed that both the average number of CAG repeats and the length of the long allele were significant predictors of osteoporotic fractures in women (P < 0.05 and P < 0.01, respectively). Men with vertebral fractures had 20.0 +/- 2.8 CAG repeats compared with 20.7 +/- 2.5 CAG repeats in normal men (ns). Linear regression analysis revealed that the length of the long allele was negatively correlated with BMD of the lumbar spine (P < 0.05) and femoral neck (P < 0.05) in women. In men, linear regression analyses demonstrated that BMD of the lumbar spine (P < 0.05), femoral neck (P < 0.05) and total hip (P < 0.05) was positively correlated with length of the CAG repeat polymorphism. In conclusion, we have demonstrated that the CAG repeat polymorphism in the first exon of the AR gene is associated with reduced bone mass and increased risk of osteoporotic fractures in women.
骨质疏松症是一种具有很强遗传因素的常见疾病。性腺功能减退会导致骨量降低，并显著增加男女患骨质疏松症的风险。因此，雌激素和雄激素受体基因是介导遗传因素对骨量及骨质疏松症风险影响的有力候选基因。雄激素受体（AR）第一个外显子中的CAG重复序列与AR转录活性降低有关。因此，我们研究了这种CAG重复序列多态性是否与284例患有椎体骨折的骨质疏松症患者及327名正常个体的骨量变化和骨质疏松性骨折风险相关。男性的CAG重复序列数量在13至30之间，女性在7至34之间。患有椎体骨折的女性和正常女性中，短等位基因和长等位基因分别包含19.2±2.5和19.0±2.3个重复序列（无显著差异），以及22.7±2.4和21.9±2.4个重复序列（P<0.01）。这种差异也反映在CAG重复序列的平均数量上：骨质疏松症女性为21.0±2.0，正常女性为20.5±2.0（P<0.05）。54.8%的骨质疏松性骨折女性与45.9%的正常女性CAG重复序列平均数量为21个及以上（χ2=3.11，P=0.08）。逻辑回归分析显示，CAG重复序列的平均数量和长等位基因的长度均是女性骨质疏松性骨折的显著预测因素（分别为P<0.05和P<0.01）。患有椎体骨折的男性CAG重复序列为20.0±2.8，正常男性为20.7±2.5（无显著差异）。线性回归分析显示，女性长等位基因的长度与腰椎（P<0.05）和股骨颈（P<0.05）的骨密度呈负相关。在男性中，线性回归分析表明，腰椎（P<0.05）、股骨颈（P<0.05）和全髋（P<0.05）的骨密度与CAG重复序列多态性的长度呈正相关。总之，我们已经证明，AR基因第一个外显子中的CAG重复序列多态性与女性骨量降低及骨质疏松性骨折风险增加有关。
