Introduction: Osteoporosis is a systemic skeletal disease with a strong genetic component. The androgen receptor (AR) is encoded by the AR gene and mediates the action of androgens, which play an important role in bone metabolism. Polymorphisms in the AR gene may be implicated in the pathogenesis of osteoporosis.
Objectives: The present study aimed to explore the influence of the (CAG)n repeat polymorphism of AR gene on BMD and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), and bone metabolic markers in a Greek female population.
Methods: Two hundred and seventeen peri- and postmenopausal women aged 4263 years were enrolled. All participants underwent spinal BMD evaluation by dual-energy X-ray absorptiometry (DXA). Genotyping of the (CAG)n repeat polymorphism was performed by PCR. Levels of OPG, soluble RANKL (sRANKL), and bone metabolic markers were measured.
Results: Genotype analysis revealed alleles having 1530 CAG repeats. The (CAG)n polymorphism was significantly associated with spinal BMD. Women having biallelic mean CAG repeat number ≥21 had significantly lower spinal BMD (0.797±0.107 g/cm2) than women having biallelic mean CAG repeat number <21 (0.841±0.129 g/cm2) (P=0.007). The association remained significant after adjustment for age, years since menopause (YSM) and BMI (P=0.016). Additionally, calcium concentration in serum was associated with the (CAG)n polymorphism. Calcium concentration in serum was higher in women with biallelic mean CAG repeat number ≥21 (9.88±0.48 mg/dl) than in women with biallelic mean CAG repeat number <21 (9.73±0.44 mg/dl) (P=0.017). No effect was observed on circulating levels of OPG and sRANKL.
Conclusions: The (CAG)n polymorphism of the AR gene may influence BMD at the lumbar spine in menopausal Greek women.