Table 1.

Candidate genes associated with osteoporosis

Candidate gene	Protein	Chromosome	Function	Reference
VDR	Vitamin D receptor	12q12-14	The nuclear hormone receptor for vitamin D3	Ferrari et al,62 Durrin et al,252 Remes et al,253 Lambrinoudaki et al,254 Wang et al,255 Pouresmaeili et al,73
ER-α	Estrogen receptor-α	6q25	An estrogen receptor	Ioannidis et al,256 Yamada et al,257 van Meurs et al,99 Tang et al,258
ER-β	Estrogen receptor-β	14q22-24	A member of the family of estrogen receptors and the superfamily of nuclear receptor transcription factors	Ogawa et al,259 Lau et al,260 Scariano et al,261 Kung et al,262
CT	Calcitonin	11p15	A peptide hormone that causes reduction in serum calcium	Miyao et al,263 Magaña et al,264
CTR	Calcitonin receptor	7q21	A high-affinity receptor for the peptide hormone calcitonin	Tural et al,265
PTH	Parathyroid hormone	11p15	This hormone elevates blood Ca2+ level by dissolving the salts in bone and preventing their renal excretion	Hosoi et al,266
PTHR	Parathyroid hormone receptor 1	3p22-21	A receptor for PTH and for PTHLH	Minagawa et al,267
CYP19	Aromatase (cytochrome P450)	15q21	A member of the cytochrome P450 superfamily of enzymes and catalyzes the last steps of estrogen biosynthesis	Napoli et al,268
CYP17	Steroid 17-alpha- hydroxylase/17,20 lyase	10q24	A member of the cytochrome P450 superfamily of enzymes and a key enzyme in the steroidogenic pathway	Zmuda et al,269 Sharp et al,270
GCR	GC receptor	5q31	Receptor for GCs that affects inflammatory responses, cellular proliferation and differentiation in target tissues	Huizenga et al,271
CaSR	Calcium-sensing receptor	3q13-21	It senses changes in the extracellular concentration of calcium ions and maintains ion homeostasis	Tsukamoto et al,272
AR	Androgen receptor	Xq11-12	A nuclear receptor that affects IGF-1 and genes involved in the development of primary and secondary male sexual characteristics expression	Langdah et al,273
TGF-β1	Transforming growth factor-β1	19q13	Potent stimulator of osteoblastic bone formation	Langdahl et al,274
IL-6	Interleukin-6	7p21	A cytokine that functions in inflammation and also as a bone- resorbing cytokine	Murray et al,108 Tsukamoto et al,109
IGF-I	Insulin-like growth factor I	12q22-24	A physiologic regulator of [1-14C]- 2-deoxy-d-glucose transport and glycogen synthesis in osteoblasts	Rivadeneira et al,275
IL-1ra	Interleukin-1 receptor antagonist	2q14	A member of the IL-1 cytokine family which inhibits the activities of IL-1	Langdahl et al,93
OPG	Osteoprotegerin	8q24	As a potent inducer of DKK-1 can inhibit the Wnt signaling pathway	Arko et al,276 García-Unzueta et al,277 Jurado et al,278
TNF-αsw	Tumor necrosis factor-α	6p21	A multifunctional bone-resorbing cytokine	Mencej et al,279
TNFR2	Tumor necrosis factor receptor 2	1p36	A member of the TNF-receptor superfamily	Hoshino et al,280
COL1A1	Collagen type Iα1	17q21-22	A fibril-forming collagen found in most connective tissues and bone	Grant et al,281 Tural et al,265
COL1A2	Collagen type Iα2	7q22	A fibril-forming collagen found in most connective tissues and bone	Lau et al,282
BGLAP	Osteocalcin	1q22	Constitutes 1%–2% of the total bone protein and binds strongly to apatite and calcium	Chen et al,283 McGuigan et al,284
MGP	Matrix Gla protein	12p12	An inhibitor of bone formation	Zebboudj et al,285
AHSG	α-2-HS-glycoprotein	3q27	Influences the mineral phase of bone	Eichner et al,286
ApoE	Apolipoprotein E	19q13	Mediates the binding, internalization and catabolism of lipoprotein particles	Johnston et al,287 Cauley et al,288
MTHFR	Methylenetetrahydrofolate reductase	1p36	Catalyzes the conversion of 5,10- methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which is used for homocysteine methylation to methionine	Villadsen et al,289
P57 (KIP2)	Cyclin-dependent kinase inhibitor 1c	11p15	Regulates osteoblast proliferation and differentiation	Urano and Inoue,290
HLA-DR15	Major histocompatibility complex, class II, DR	6p21	Interacts with another gene related to bone metabolism such as TNF-α	Douroudis et al,291
PPARγ	Peroxisome proliferator- activated receptor-γ	3p25	Key regulator of adipocyte differentiation and glucose homeostasis	Altshuler et al,292
FRA-1	Fos-related antigen-1	11q13	Leucine zipper proteins that act as regulators of cell proliferation, differentiation and transformation	Albagha et al,293
RUNX-2	Runt-related transcription factor-2	6p21	Essential for osteoblastic differentiation and skeletal morphogenesis	Vaughan et al,294 Doecke et al,295
Klatho gene	Klotho protein	13q12	Involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D	Kawano et al,296
WRN (Werner syndrome gene)	Werner helicase	8p12	A DNA helicase involved in many aspects of DNA metabolism	Ogata et al,297
LRP5	Receptor related protein 5	11q12-13	A coreceptor with frizzled protein family members for transducing signals by Wnt proteins	Babij et al,298 Ai et al,299
CTSK	Cathepsin K	1q21	A lysosomal cysteine proteinase involved in bone remodeling and resorption	Giraudeau et al,300
BMP4	Bone morphogenetic protein 4	14q22	It plays an important role in the onset of endochondral bone formation in humans	Babu et al,301
CLCN7	Chloride channel 7	16p13	Slow voltage-gated channel mediating the exchange of chloride ions against protons	Pettersson et al,302 Kornak et al,303
TCIRG1	T cell immune regulator	11q13.4-q13.5	Part of the proton channel of V-ATPases	Lee et al,304
FDPS	Farnesyl pyrophosphate synthase	1q22	Key enzyme in isoprenoid biosynthesis	Marini et al,305
P2X7	Purinergic receptor P2X, ligand-gated ion channel, 7	12q24	Found in the central and peripheral nervous systems and increases the release of proinflammatory molecules such as IL-1β, IL-6 and TNF-α	Gartland et al,306

Abbreviations: GC, glucocorticoid; IGF, insulin-like growth factor; IL, interleukin; PTH, parathyroid hormone; PTHLH, parathyroid hormone-like hormone; TNF, tumor necrosis factor.