AbstractObjectiveOsteoporosis and obesity are complex diseases with a strong genetic component. Bone mineral density (BMD) and body mass index (BMI) linkage studies identified a locus at 1q21-23, where the interleukin-6 receptor (IL6R) gene is located. The IL6R and the gp130 receptors are the mediators of IL6 action. Serum levels of IL6 and sIL6R (the soluble form of IL6R) are higher in several diseases such as osteoporosis or obesity. Variants atIL6Rhave been associated with BMI and obesity. However,IL6Ris an as-yet-unexplored osteoporosis candidate gene.DesignIn the present study we analysed two polymorphisms in theIL6Rpromoter, −1435 C/T (rs3887104) and −208 G/A (rs4845617), and the Asp358Ala polymorphism (rs8192284), in relation to both BMD and BMI in a cohort of 559 postmenopausal Spanish women.ResultsThe promoter polymorphisms, −1435 C/T and −208 G/A were associated with femoral neck (FN) BMD (P=0.011 andP=0.025 respectively). The C-A and T-G promoter haplotypes were also associated with FN BMD. Additionally, the Asp358Ala variant was associated with lumbar spine BMD (P=0.038). Finally, the −208 G/A polymorphism and the C-G and C-A haplotypes were associated with BMI and obesity, where GG was the risk genotype (P=0.033 for BMI;P=0.010 for obesity).ConclusionThese data suggest that variants in theIL6Rgene are not only involved in the determination of BMI but also relevant for the determination of BMD. TheIL6Rgene may belong to the growing list of genes known to be involved in both phenotypes.