Serum Calcium Concentration Is Associated with Bone Mineral Density and Synonymous Variants in the RYR1 Gene in a Mexican-Mestizo Population

Resumen

Background/Objectives: Serum calcium concentrations have been associated with bone mineral density (BMD), but results seem to depend on sex. Genetic variants in the Ryanodine Receptor1 (RYR1) gene have been previously associated with low BMD in postmenopausal women. Serum RYR1 concentration was found to be higher in osteopenia and osteoporosis groups. The function and biological relevance of RYR1 in bone remodeling remains unknown. This cross-sectional study explored the relationship between serum calcium concentrations, BMD, and genetic variants in RYR1 in a Mexican-mestizo population. Methods: Serum samples from 966 participants were obtained from the third measurement of the Health Workers Cohort Study (HWCS) 2017–2019, conducted by the Mexican Social Security Institute (IMSS). All participants included in this study were of Mexican Mestizo origin and had data on BMD. We measured ionized calcium and genotyped the genetic variants rs2288888 (g.38455542G>A) and rs11083462 (g.38469040C>T) of the RYR1 gene. BMD of the total hip, lumbar spine, and femoral neck was measured using a Lunar DPX NT DEXA device. Results: Our results show that elevated serum calcium concentrations in females are associated with lower BMD at the hip and femoral neck. In contrast, higher calcium concentrations in males were associated with greater total hip BMD. In our study, the variants rs2288888 and rs11083462 were associated with higher serum calcium concentrations (under-adjusted and unadjusted data) in males but not females. Conclusions: Serum calcium levels are associated with BMD, depending on sex. The RYR1 gene variants rs2288888 and rs11083462 may have a protective effect in men.