Genetic variants in obesity-related genes and the risk of osteoporotic fracture. The Hortega Follow-up Study.

Background: Osteoporosis and obesity are major public health problems that are closely correlated, as they share various features, including a genetic predisposition. A genetic correlation between obesity and osteoporosis due to the biological common pathways of bone and fat metabolism, which implies pleiotropic genes regulating has been described. The objective of our study was to analyse whether polymorphisms in obesity-related genes modify the risk of osteoporotic bone fracture.

Methods: We studied 575 subjects from the Hortega Study. The subjects were followed-up for 12-14 years. 202 subjects were overweight, 143 obese and 221 had bone fractures. The distribution of 39 genetic variants in 22 obesity-related genes were studied.

Results: The results showed a relationship between polymorphisms in the and genes and the susceptibility to osteoporotic fracture. The variant genotype of the rs2568958 polymorphism and the rs6499649, rs3751812, and rs8044769 genetic variants in were associated with susceptibility to bone fracture. In the best of our knowledge, this is the first time that these variants in and genes have been associated with the susceptibility to osteoporotic bone fracture, supporting the hypothesis that the and genes might be candidates for osteoporosis and bone fracture.

Conclusions: In conclusion, this study associates obesity-related polymorphisms in the and genes with osteoporotic bone fracture, reinforcing the hypothesis that obesity and bone metabolism are closely correlated genetically.