Polymorphisms in the CLCN7 Gene Modulate Bone Density in Postmenopausal Women and in Patients with Autosomal Dominant Osteopetrosis Type II

Context: Genetic factors are important determinants of bone mineral density (BMD). The fact that mutations in the ClC-7 chloride channel cause autosomal dominant osteopetrosis (ADOII) make the CLCN7 gene an attractive candidate for the regulation of bone density. Objective: The objective of the study was to investigate the association between polymorphisms in the CLCN7 gene and BMD in postmenopausal women and with clinical variability in ADOII. Design: This was a genetic association study using five single-nucleotide polymorphisms and a variable number tandem repeat (VNTR) polymorphism in the CLCN7 gene. Participants: A total of 425 postmenopausal women aged 64 ± 7 yr participated in the study. We also investigated an ADOII family with low penetrance comprising 18 mutation carriers. Main Outcome Measure(s): In our postmenopausal cohort, individual single-nucleotide polymorphism genotypes and haplotypes were analyzed for association with BMD at the lumbar spine and the femoral neck and with the bone resorp...