Table 1.
Major candidate genes tested for association with osteoporosis-related phenotypes
| Candidate genes | Protein | Chromosome location |
|---|---|---|
| Calciotropic hormones and receptors | ||
| AR | Androgen receptor | Xq11.2-q12 |
| CASR | Calcium-sensing receptor | 3q13 |
| CRHR1 | Corticotropin-releasing hormone receptor 1 | 17q12-q22 |
| CTR | Calcitonin receptor | 7q21.3 |
| CYP17A1 | Steroid 17-α-hydroxylase | 10q24.3 |
| CYP19 | Cytochrome P450, family XIX | 10q26 |
| CYP19A1 | Aromatase | 15q21.1 |
| CYP1B1 | Aryl hydrocarbon hydroxylase | 2p21 |
| DBP | Vitamin D-binding protein | 4q12-q13 |
| ER-a | Estrogen receptor-a | 6q25.1 |
| ER-b | Estrogen receptor-b | 14q23.2 |
| ESRRA | Estrogen-related receptor α | 11q13 |
| GR | Glucocorticoid receptor | 5q31.3 |
| LHB | Luteinizing hormone β polypeptide | 19q13.32 |
| LHCGR | Luteinizing hormone-choriogonadotropin receptor | 2p21 |
| PRL | Prolactin | 6p22.2-p21.3 |
| PTH | Parathyroid hormone | 11p15.3-p15.1 |
| PTHLH | Parathyroid hormone-like hormone | 12p12.1-p11.2 |
| PTHR1 | Parathyroid hormone receptor 1 | 3p22-p21.1 |
| PTHR2 | Parathyroid hormone receptor 2 | 2q33 |
| SHBG | Sex hormone-binding globulin | 17p13-p12 |
| SRD5A2 | Steroid-5-α-reductase, α polypeptide 2 | 2p23 |
| TSHR | Thyroid-stimulating hormone receptor | 14q31 |
| VDR | Vitamin-D receptor | 12q13.11 |
| Cytokines, growth factors, and receptors | ||
| BMP2 | Bone morphogenetic protein 2 | 20p12 |
| BMP7 | Bone morphogenetic protein 7 | 20q13 |
| CD40 | Tumor necrosis factor receptor superfamily member 5 | 20q12-q13.2 |
| CNR2 | Cannabinoid receptor 2 | 1p36.11 |
| DKK2 | Dickkopf homolog 2 | 4q25 |
| FGFR1 | Fibroblast growth factor receptor 1 | 8p11.2-p11.1 |
| FGFR2 | Fibroblast growth factor receptor 2 | 10q26 |
| GDF5 | Growth differentiation factor 5 | 20q11.2 |
| GHRH | Growth hormone-releasing hormone | 20q11.2 |
| IGFBP2 | Insulin-like growth factor binding protein 2 | 2q33-q34 |
| IL-23 | Interleukin 23 | 12q13.2 |
| IL-23R | Interleukin 23 receptor | 1p31.3 |
| IL-6 | Interleukin 6 | 7p21 |
| IL-6R | Interleukin 6 receptor | 1q21 |
| IL-15 | Interleukin 15 | 4q31 |
| LEPR | Leptin receptor | 1p31 |
| LRP1 | Low-density lipoprotein receptor-related protein 1 | 12q13-q14 |
| LRP5 | Low-density lipoprotein receptor-related protein 5 | 11q13.4 |
| LRP6 | Low-density lipoprotein receptor-related protein 6 | 12p11-p13 |
| LTBP2 | Latent transforming growth factor β binding protein 2 | 14q24 |
| MSTN | Myostatin | 2q32.2 |
| NPY | Neuropeptide Y | 7p15.1 |
| OPG | Osteoprotegerin | 8q24 |
| RANK | Receptor activator of nuclear factor κ-β | 18q22.1 |
| RANKL | Receptor activator of nuclear factor κ-β ligand | 13q14 |
| TGF-b1 | Transforming growth factor b-1 | 19q13.1 |
| TNF-a | Tumor necrosis factor a | 6p21.3 |
| TNFRSF1B | Tumor necrosis factor receptor superfamily, member 1B | 1p36.3-p36.2 |
| TNF-β | Lymphotoxin α | 6p21.3 |
| VEGF | Vascular endothelial growth factor A | 6p12 |
| Bone matrix proteins | ||
| COL1A1 | Collagen type I α-1 | 17q21.33 |
| COL1A2 | Collagen type I α-2 | 7q22.1 |
| ITGA1 | Integrin, α 1 | 5q11.2 |
| MMP2 | Matrix metallopeptidase 2 | 16q13-q21 |
| OCIL | Osteoclast inhibitory lectin | 12p13 |
| SPARC | Osteonectin | 5q31.3-q32 |
| (Continued) | ||
| Candidate genes |
Protein |
Chromosome location |
| Miscellaneous | ||
| ADCY10 | Adenylate cyclase 10 | 1q24 |
| ALOX15 | Arachidonate 15-lipoxygenase | 17p13.3 |
| ALOX5 | Arachidonate 5-lipoxygenase | 10q11.2 |
| ALPL | Alkaline phosphatase | 1p36.12 |
| ANXA6 | Annexin A6 | 5q32-q34 |
| APC | Adenomatous polyposis coli | 5q21-q22 |
| ARHGEF3 | Rho guanine nucleotide exchange factor 3 | 3p21-p13 |
| BMPR1B | Bone morphogenetic protein receptor, type IB | 4q22-q24 |
| CA10 | Carbonic anhydrase X | 17q21.33 |
| CA8 | Carbonic anhydrase VIII | 8q11-q12 |
| CALM1 | Calmodulin 1 | 14q24-q31 |
| CLCN7 | Chloride channel 7 | 16p13 |
| COMT | Catechol-O-methyltransferase | 22q11.21 |
| CRTAP | Cartilage-associated protein | 3p22.3 |
| DMP1 | Dentin matrix acidic phosphoprotein 1 | 4q21 |
| ENPP1 | Ectonucleotide pyrophosphatase/phosphodiesterase 1 | 6q22-q23 |
| FABP3 | Fatty acid-binding protein 3 | 1p33-p32 |
| FLNB | Filamin β | 3p14.3 |
| FLT1 | Fms-related tyrosine kinase 1 | 13q12 |
| FOXC2 | Forkhead box C2 | 16q22-q24 |
| FZD1 | Frizzled homolog 1 | 7q21 |
| FZD6 | Frizzled homolog 6 | 8q22.3-q23.1 |
| HMGA2 | High mobility group AT-hook 2 | 12q15 |
| HOXA | Homeobox A cluster | 7p15-p14 |
| HSD11B1 | Hydroxysteroid (11-β) dehydrogenase 1 | 1q32-q41 |
| MDR1 | Multidrug resistance 1 | 7q21.1 |
| MTHFR | Methylenetetrahydrofolate reductase | 1p36.3 |
| NFATC1 | Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 | 18q23 |
| NOG | Noggin | 17q21-q22 |
| NOS3 | Endothelial nitric oxidase synthase | 7q36 |
| NR1I3 | Constitutive androstane receptor | 1q23.3 |
| P2X 7 | Purinergic receptor P2X, ligand-gated ion channel, 7 | 12q24 |
| PBX1 | Pre-B-cell leukemia homeobox 1 | 1q23 |
| PIR | Pirin | Xp22.2 |
| PLOD | Procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1 | 1p36.22 |
| PPAR-g | Peroxisome proliferator-activated receptor γ | 3p25 |
| PTN | Pleiotrophin | 7q33-q34 |
| RIZ1 | Retinoblastoma protein-interacting zinc finger protein | 1p36.21 |
| ROR2 | Receptor tyrosine kinase-like orphan receptor 2 | 9q22 |
| RUNX2 | Runt-related transcription factor 2 | 6p21 |
| SFRP1 | Secreted frizzled-related protein 1 | 8p12-p11.1 |
| SFRP2 | Secreted frizzled-related protein 2 | 4q31.3 |
| SOST | Sclerostin | 17q11.2 |
| SREBF1 | Sterol regulatory element binding transcription factor 1 | 17p11.2 |
| THSD4 | Thrombospondin, type I, domain containing 4 | 15q23 |
| THSD7 | Thrombospondin, type I, domain containing 7A | 7p21.3 |
| TIMP2 | Tissue inhibitor of metalloproteinase 2 | 17q25 |
| TWIST1 | Twist homolog 1 | 7p21.2 |
| WISP3 | WNT1 inducible signaling pathway protein 3 | 6q21 |
| WNT10B | Wingless-type MMTV integration site family, member 10B | 12q13 |
| WNT3A | Wingless-type MMTV integration site family, member 3A | 1q42 |
| WNT7B | Wingless-type MMTV integration site family, member 7B | 22q13 |
Adapted from Y. Guo et al.: Expert Rev Endocrinol Metab 3:223–267, 2008 (3), with permission from Expert Reviews Ltd. MMTV, Mouse mammary tumor virus.