Pharmacogenomics in osteoporosis: Steps toward personalized medicine

Figures & data

Figure 1 Risk factors and risk of fracture management.

Table 1 Pharmacogenetics and pharmacogenomics in osteoporosis

Vitamin D receptor (VDR) The BsmI, ApaI, TaqI, and FokI polymorphisms have been extensively studied with large meta-analyses showing no association with BMD or a modest effect. The Cdx2 polymorphism was shown to have a modest effect on the risk of vertebral fracture in a meta-analysis.

Estrogen receptor (ERα and ERβ) gene The XbaI and PvuII polymorphisms have been extensively studied in the ERα gene. Meta-analyses have demonstrated association with BMD and fracture risk with the XbaI polymorphism. There have been inconclusive results with both polymorphisms and more research is needed.

Type I collagen (COLIA1) gene A polymorphism affecting the Sp1 binding site has been extensively studied. An association between fracture risk and the Sp1 polymorphism has been determined and backed by large meta-analyses. It is likely that COLIA1 polymorphisms play more of a role in bone quality and fracture risk.

Aromatase (CYP19) gene A TTTA repeat polymorphism has been the most extensively studied in the CYP19 gene. Short TTTA alleles have been associated with lower BMD in women. No consistent picture of CYP19 gene polymorphisms can be shown at present because of conflicting evidence.

Calcium-sensing receptor (CaSR) gene The CaSR gene A986S has been shown to have no effect in postmenopausal women related to BMD. Larger studies are needed but as of now there is not enough evidence proving the CaSR gene will play a major role in the pharmacogenomics of osteoporosis.

Low-density lipoprotein receptor-related protein 5 (LRP5) gene The variants Val667Met and Ala330Val were found to be associated with BMD and fracture risk in a meta-analysis. More studies are needed to determine the role of LRP5 affecting BMD and osteoporosis.

Interleukin-6 (IL-6) gene Functional polymorphisms in the IL-6 promoter region, −572 GC and −174 GC were shown to be associated with markers of bone resorption in postmenopausal women. Larger, better studies are needed as the results are still inconclusive.

Calcitonin receptor (CTR) The calcitonin gene polymorphism 108 bp was found to be associated with a positive change in BMD after hormone therapy in Korean women. There is a lack of studies and inconclusive results with the calcitonin receptor gene and its role in the pharmacogenomics of osteoporosis.

Androgen receptor (AR) gene A Danish study found an association between the (CAG)n repeat polymorphism in postmenopausal women with bone mass. There is a lack of studies and data on the androgen receptor and results are inconclusive.

P2X7 gene A loss-of-function SNP in the P2X7 gene has been recently discovered to play a role in osteoclast activity and bone fragility. The P2X7 Glu496Ala and the Ile568Asn SNPs are associated with fracture risk and response to hormone replacement therapy. Larger studies are needed to determine if this gene will be useful in the pharmacogenomics of osteoporosis.

Methylenetetrahydrofolate reductase (MTHFR) gene The polymorphism C677T has been studied in the MTHFR gene. Association has been inconsistent and larger, better studies are needed in future.

Abbreviation: BMD, bone mineral density.