Genome-Wide Association Study of Bone Mineral Density in Premenopausal European-American Women and Replication in African-American Women

Koller, Daniel L.; Ichikawa, Shoji; Lai, Dongbing; Padgett, Leah R.; Doheny, Kimberly F.; Pugh, Elizabeth; Paschall, Justin; Hui, Siu L.; Edenberg, Howard J.; Xuei, Xiaoling; Peacock, Munro; Econs, Michael J.; Foroud, Tatiana

doi:10.1210/jc.2009-1903

Cited by 76 publications

(60 citation statements)

References 29 publications

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“…Although the peak level of BMD is influenced by diet and physical activity, genetic factors are also important. Studies about this issue showed that ADAMTS18 has been associated with femoral neck bone mineral density (41).…”

Section: Menopause and Adamtsmentioning

confidence: 99%

A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

Demircan

Cömertoğlu

Akyol

et al. 2014

J Turkish German Gynecol Assoc

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Review 250Introduction A Disintegrin-like and Metalloproteinase with Thrombospondin type-1 motif (ADAMTS) proteinases, which are released outside the cell (soluble), have very critical roles in damage and repair of extracellular matrix (ECM) processes (remodeling) (1). The ADAMTS family, which degrades ECM structural substrates, such as collagen, aggrecan and versican, has 19 family members (2). These enzymes, which are associated with a great deal of vital physiological processes in the ECM, are inhibited by tissue inhibitors of metalloproteinases (TIMPs) (3, 4). Family members of this group are divided into various subgroups according to their tasks in the ECM (Figure 1). ADAMTS1 (METH-1), which was identified for the first time in colon adenocarcinoma, is associated with inflammation (5) and shows anti-angiogenic properties with ADAMTS8 (METH-2) (6, 7). Especially in the physiology of ovulation, there is interest in these proteases. ADAMTS1 also takes important roles in the process of normal growth, fertility, and organogenesis (8). ADAMTS 2, 3, and 14, also known pro-collagen N-proteinases, have important roles in collagen synthesis in the ECM. Various connective tissue diseases are seen in ADAMTS2 deficiency in this group (9). ADAMTS1, -4, -5, -8, -9, -15, -16, and -18 degrade aggrecan, which is the one of the main components of the ECM; so, they are called as aggrecanases (1). ADAMTS1, -4, and -5 degrade brevican and versican, other structural ECM components (10). Versican helps hyaluronan, which is the basic element of the ECM, to stabilize the matrix (11). ADAMTS5 and -6, expressed specifically in the placenta, are thought to be responsible for implantation (12). ADAMTS7 and -12 degrade Cartilage oligomeric matrix protein (COMP), which is an essential glycoprotein in cartilage matrix (13). ADAMTS10 has important roles in the development of tissues of skin and lens. In ADAMTS10 mutations, autosomal recessive Weill-Marchesani syndrome is seen (14). Known as von Willebrand cleaving protease, ADAMTS13 has effects on coagulation and homeostasis. This protease degrades ultralarge VWF multimers that are localized in endothelial surfaces; so, it prevents thrombus formation (9). Thrombotic thrombocytopenic purpura (TTP), a serious problem during pregnancy, occurs in ADAMTS13 deficiency (15). Increased by follicle-stimulating hormone (FSH) and luteinizing hormone (LH), ADAMTS16 degrades a-2 macroglobulin in the ECM (16). ADAMTS17 is involved in estrogen-induced apoptosis in cancer cells (16). ADAMTS9 and -20 are known Playing a key role in the pathophysiology of many diseases, A Disintegrin-like and Metalloproteinase with Thrombospondin type-1 motif (AD-AMTS) proteinases have been attracted more attention in obstetrics and gynecology. First discovered in 1997, this zinc-dependent proteinase family has 19 members today. These enzymes, which are located in the extracellular matrix (ECM), have a lot of very important functions, like matrix formation and resorption, angiogenesis, ovulation, and coagulation. In additio...

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Section: Menopause and Adamtsmentioning

confidence: 99%

A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

Demircan

Cömertoğlu

Akyol

et al. 2014

J Turkish German Gynecol Assoc

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“…Estrogen receptor 1 (ESR1) at 6q25.1, (5)(6)(7)(8) low density lipoprotein receptor-related protein 4 (LRP4) at 11p11.2, (7)(8)(9) low density lipoprotein receptor-related protein 5 (LRP5) at 11q13.4, (6)(7)(8)10,11) integrin, alpha 1 (ITGA1) at 5q11.2, (8) secreted phosphoprotein 1ADAM metallopeptidase with thrombospondin type 1 motif 18 (ADAMTS18) at 16q23, (16,17) and spectrin, beta, non-erythrocytic 1 (SPTBN1) at 2p21 (5,7,9,12,18) are associated with BMD at the GWAS level. Among them, the associations between variants in ZBTB40, (10) ESR1, (10) TNFRSF11B, (10) LRP5, (10) ADAMTS18, (16) and SPTBN1 (12,18) and osteoporosis have been replicated in both European and East-Asian populations.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility genes for osteoporotic fracture in postmenopausal chinese women

Wang

Zeng

Zhang

et al. 2012

Journal of Bone and Mineral Research

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To identify the susceptibility genes for osteoporotic fracture in postmenopausal Chinese women, a two-stage case-control association study using joint analysis was conducted in 1046 patients with nontraumatic vertebra, hip, or distal radius fractures and 2303 healthy controls. First, 113 single-nucleotide polymorphisms (SNPs) in 16 potential osteoporosis candidate genes reported in recent genomewide association studies, meta-analyses studies, large-scale association studies, and functional studies were genotyped in a smallsample-size subgroup consisting of 541 patients with osteoporotic fractures and 554 healthy controls. Variants and haplotypes in SPTBN1, TNFRSF11B, CNR2, LRP4, and ESR1 that have been identified as being associated with osteoporotic fractures were further reanalyzed in the entire case-control group. We identified one SNP in TNFRSF11B (rs3102734), three SNPs in ESR1 (rs9397448, rs2234693, and rs1643821), two SNPs in LRP4 (rs17790156 and rs898604), and four SNPs in SPTBN1 (rs2971886, rs2941583, rs2941584, and rs12475342) were associated with all of the broadly defined osteoporotic fractures. The most significant polymorphism was rs3102734, with increased risk of osteoporotic fractures (odds ratio, 1.35; 95% confidence interval [CI], 1.17-1.55, Bonferroni p ¼ 2.6 Â 10 À4 ). Furthermore, rs3102734, rs2941584, rs12475342, rs9397448, rs2234693, and rs898604 exhibited significant allelic, genotypic, and/or haplotypic associations with vertebral fractures. SNPs rs12475342, rs9397448, and rs2234693 showed significant genotypic associations with hip fractures, whereas rs3102734, rs2073617, rs1643821, rs12475342, and rs2971886 exhibited significant genotypic and/or haplotypic associations with distal radius fractures. Accordingly, we suggest that in addition to the clinical risk factors, the variants in TNFRSF11B, SPTBN1, ESR1, and LRP4 are susceptibility genetic loci for osteoporotic fracture in postmenopausal Chinese women. ß

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“…Despite the importance of IBSP, encoding for bone sialoprotein 2, in various aspects of bone physiology [44], this gene has been poorly studied as a candidate in the association studies of relevant phenotypes. Thus we are aware of only two studies where IBSP gene was investigated and specifically mentioned within the framework of genetic association studies [45,46]. Both studies were designed as genome-wide association study of BMD and both provided evidence of importance of IBSP in determination of BMD.…”

Section: Discussionmentioning

confidence: 99%

“…The median levels of OPN were significantly higher in men than in women, 51.725 vs. 46.200 ng/ml (Mann-Whitney U test, p=0.022). There were significant but modest correlations between age and OPN levels in the total sample (r=0.0848, p=0.010) and in the females' sample (r=0.1776, p<0.001).…”

Section: Preliminary Statisticsmentioning

confidence: 90%

Quantitative genetic study of the circulating osteopontin in community-selected families

et al. 2010

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Genome-Wide Association Study of Bone Mineral Density in Premenopausal European-American Women and Replication in African-American Women

Abstract: Evidence of association to several novel loci was detected in a GWAS of premenopausal EA women, and SNPs in one of these loci also provided supporting evidence in a sample of AA women.

Cited by 76 publications

References 29 publications

A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

Susceptibility genes for osteoporotic fracture in postmenopausal chinese women

Quantitative genetic study of the circulating osteopontin in community-selected families

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