Genetic factors play an important role in the regulation of bone mass and in the pathogenesis of osteoporosis. Twin and family studies have shown that 50–85% of the variance in BMD is determined genetically, and molecular genetic studies have identified several candidate genes and quantitative trait loci that are involved in this process.
The most widely studied candidate genes are the vitamin D receptor (VDR) gene, the estrogen receptor alpha gene, and the COLIA1 gene, which encodes the alpha 1 chain of type I collagen. There is evidence to suggest that allelic variation in all three genes plays a role in regulating BMD, but the effects are modest and together probably account for less than 5% of the heritable contribution to BMD. The COLlAI Sp1 binding site polymorphism acts as a marker for osteoporotic fractures, independent from its association with BMD, and is associated with altered collagen production by bone cells and reduced bone strength.
Linkage studies support the view that BMDregulation is under polygenic control in that they have identified multiple quantitative trait loci for regulation of BMD in humans and experimental animals.
Most of the genes responsible for the heritable component of BMD regulation and genetic effects on fracture risk remain to be discovered. When this information becomes available, it is likely that genetic testing for candidate gene polymorphisms will be used clinically in the assessment of osteoporotic fracture risk and in predicting treatment response.
KeywordsBone Mineral Density Quantitative Trait Locus Bone Mass Osteoporotic Fracture Osteogenesis Imperfecta
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