Genetic regulation of bone mass and susceptibility to osteoporosis

被引:250
作者
Ralston, Stuart H. [1 ]
de Crombrugghe, Benoit
机构
[1] Western Gen Hosp, Mol Med Ctr, Rheumat Dis Unit, Edinburgh EH4 2XU, Midlothian, Scotland
[2] Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA
关键词
human molecular genetics; linkage; osteoporosis; association studies;
D O I
10.1101/gad.1449506
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and increased risk of fragility fractures. Twin and family studies have shown that the heritability of bone mineral density (BMD) and other determinants of fracture risk such as ultrasound properties of bone, skeletal geometry, and bone turnover - is high, although heritability of fracture is modest. Many different genetic variants of modest effect size are likely to contribute to the regulation of these phenotypes by interacting with environmental factors such as diet and exercise. Linkage studies in rare Mendelian bone diseases have identified several previously unknown genes that play key roles in regulating bone mass and bone turnover. In many instances, subtle polymorphisms in these genes have also been found to regulate BMD in the general population. Although there has been extensive progress in identifying the genetic variants that regulate susceptibility to osteoporosis, most of the genes and genetic variants that regulate bone mass and susceptibility to osteoporosis remain to be discovered.
引用
收藏
页码:2492 / 2506
页数:15
相关论文
共 135 条
[111]   GENETIC FACTORS IN DETERMINING BONE MASS [J].
SMITH, DM ;
NANCE, WE ;
KANG, KW ;
CHRISTIAN, JC ;
JOHNSTON, CC .
JOURNAL OF CLINICAL INVESTIGATION, 1973, 52 (11) :2800-2808
[112]   Genes control the cessation of a woman's reproductive life: A twin study of hysterectomy and age at menopause [J].
Snieder, H ;
MacGregor, AJ ;
Spector, TD .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (06) :1875-1880
[113]   Association between a polymorphism affecting an AP1 binding site in the promoter of the TCIRG1 gene and bone mass in women [J].
Sobacchi, C ;
Vezzoni, P ;
Reid, DM ;
McGuigan, FEA ;
Frattini, A ;
Mirolo, M ;
Albhaga, OME ;
Musio, A ;
Villa, A ;
Ralston, SH .
CALCIFIED TISSUE INTERNATIONAL, 2004, 74 (01) :35-41
[114]   Association of COLIA1 Sp1 alleles with defective bone nodule formation in vitro and abnormal bone mineralization in vivo [J].
Stewart, TL ;
Roschger, P ;
Misof, BM ;
Mann, V ;
Fratzl, P ;
Klaushofer, K ;
Aspden, R ;
Ralston, SH .
CALCIFIED TISSUE INTERNATIONAL, 2005, 77 (02) :113-118
[115]  
STEWART TL, 2006, IN PRESS J CLIN ENDO
[116]   Linkage of osteoporosis to chromosome 20p12 and association to BMP2 [J].
Styrkarsdottir, U ;
Cazier, JB ;
Kong, A ;
Rolfsson, O ;
Larsen, H ;
Bjarnadottir, E ;
Johannsdottir, VD ;
Sigurdardottir, MS ;
Bagger, Y ;
Christiansen, C ;
Reynisdottir, I ;
Grant, SFA ;
Jonasson, K ;
Frigge, ML ;
Gulcher, JR ;
Sigurdsson, G ;
Stefansson, K .
PLOS BIOLOGY, 2003, 1 (03) :351-360
[117]   Meta-analysis of molecular association studies: Vitamin D receptor gene polymorphisms and BMD as a case study [J].
Thakkinstian, A ;
D'Este, C ;
Eisman, J ;
Nguyen, T ;
Attia, J .
JOURNAL OF BONE AND MINERAL RESEARCH, 2004, 19 (03) :419-428
[118]  
Torgerson DJ, 1996, J BONE MINER RES, V11, P293
[119]   Congenic mice reveal sex-specific genetic regulation of femoral structure and strength [J].
Turner, CH ;
Sun, Q ;
Schriefer, J ;
Pitner, N ;
Price, R ;
Bouxsein, ML ;
Rosen, CJ ;
Donahue, LR ;
Shultz, KL ;
Beamer, WG .
CALCIFIED TISSUE INTERNATIONAL, 2003, 73 (03) :297-303
[120]   Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites [J].
Uitterlinden, AG ;
Arp, PP ;
Paeper, BW ;
Charmley, P ;
Proll, S ;
Rivadeneira, F ;
Fang, Y ;
van Meurs, JBJ ;
Britschgi, TB ;
Latham, JA ;
Schatzman, RC ;
Pols, HAP ;
Brunkow, ME .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (06) :1032-1045