High-Density Association Study of 383 Candidate Genes for Volumetric BMD at the Femoral Neck and Lumbar Spine Among Older Men

Yerges, Laura M.; Klei, Lambertus; Cauley, Jane A.; Roeder, Kathryn; Kammerer, Candace M.; Moffett, Susan P.; Ensrud, Kristine E.; Nestlerode, Cara S.; Marshall, Lynn M.; Hoffman, Andrew R.; Lewis, Cora E.; Lang, Thomas; Barrett‐Connor, Elizabeth; Ferrell, Robert E.; Orwoll, Eric; Zmuda, Joseph M.

doi:10.1359/jbmr.090524

Cited by 59 publications

(50 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…rs1513670 polymorphisms of SOST are found to be associated with total hip BMD in healthy Shanghai women [30], but we fail to find this association. We reveal rs851054 polymorphisms of SOST gene significantly correlated to lumbar spine BMD, which are consistent with findings in old American men and postmenopausal Australian women [23,34], but do not conform to results in Korean and Spanish postmenopausal population [36,37].…”

Section: Discussionsupporting

confidence: 69%

See 1 more Smart Citation

SOST Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women With Osteoporosis

Zhou

Zhang

et al. 2015

Pharmacogenomics

View full text Add to dashboard Cite

Aim:To investigate the association between SOST gene polymorphisms and response to alendronate treatment. Materials & methods: 639 Chinese postmenopausal women with osteoporosis or osteopenia received alendronate treatment. Polymorphisms of SOST were analyzed. Bone mineral density (BMD), serum ALP and β-CTX levels were measured. The correlation of SOST polymorphisms with changes of BMD and bone biomarkers after treatment was analyzed. Results: rs1234612 and rs851054 polymorphisms were correlated to baseline lumbar spine BMD (p < 0.05). After 12 months of treatment rs1234612 and rs865429 polymorphisms were correlated to BMD changes at the lumbar spine (p < 0.05) or femoral neck (p < 0.05), respectively. Conclusion: The polymorphisms of SOST are genetic factors affecting bone health and response to alendronate in Chinese postmenopausal women.

show abstract

Section: Discussionsupporting

confidence: 69%

“…Compliance to alendronate was evaluated by the number of empty medicine bottles and the remaining tablets at each follow-up. [23,24]. Finally, six tag SNPs and one positive SNP of SOST were selected: rs1234612, rs851054, rs865429, rs851062, rs1513670, rs9902563 and rs1877632 (Supplementary Table 1).…”

Section: Study Participantsmentioning

confidence: 99%

SOST Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women With Osteoporosis

Zhou

Zhang

et al. 2015

Pharmacogenomics

View full text Add to dashboard Cite

show abstract

“…In addition, most of these studies have been conducted in women. In contrast, in a relatively large study of men, no significant association was observed between these three genes and volumetric BMD at the femoral neck and lumbar spine (LS) (34) or trabecular and cortical volumetric BMD at the femoral neck. (35) Nevertheless, recently, SNPs located near RANKL, (36) RANK, (37) and OPG (36,38) also have been associated with BMD in genome-wide association studies (GWAS).…”

Section: Introductionmentioning

confidence: 87%

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

Roshandel

Holliday

Pye

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r 2 ! 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMD a ) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP rs9594759 (C) was associated with lower PINP (b ¼ À1.84, p ¼ .003) and CTX-I (b ¼ À27.02, p ¼ 6.06 Â 10 À8 ) and higher ultrasound BMD at the calcaneus (b ¼ 0.01, p ¼ .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. ß

show abstract

“…Despite this, little information is available regarding the adult skeletal consequences of severe THRA mutations, whilst no individuals with less deleterious THRA mutations or patients with DIO2 mutations have been described. A candidate gene association study of 862 men over 65 years of age investigated the relationships between genetic variation in THRA and BMD at the femoral neck and lumbar spine (25,26), whilst a much larger study investigated the THRA locus in relation to BMD, fracture risk and bone geometry in 27 326 individuals from the Genetic Factors for Osteoporosis (GEFOS) consortium and the Rotterdam Study 1 and 2 populations (21). These studies did not identify any relationships between variation in bone parameters and genetic variation across the THRA locus.…”

Section: Discussionmentioning

confidence: 99%

THRA and DIO2 mutations are unlikely to be a common cause of increased bone mineral density in euthyroid post-menopausal women

Gogakos

Logan

Waung

et al. 2014

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: A new autosomal dominant disorder due to mutation of THRA, which encodes thyroid hormone receptor a, is characterised by severely delayed skeletal development but only slightly abnormal thyroid status. Adult mice with disrupted thyroid hormone action in bone due to a mutation of Thra or deletion of Dio2, encoding the type 2 deiodinase, have high bone mass and mineralisation despite essentially euthyroid status. No individuals with DIO2 mutations have been described and the adult phenotype of patients with THRA mutations is largely unknown. We hypothesised that screening euthyroid adults with high bone mineral density (BMD) could be used to identify individuals with mutations of THRA or DIO2. Design: The Osteoporosis and Ultrasound Study (OPUS) is a 6-year prospective study of fracture-related factors from five European centres. Methods: A cohort of 100 healthy euthyroid post-menopausal women with the highest BMD was selected from the OPUS population. We sequenced the intron-exon boundaries and critical exons of THRA and DIO2 in these subjects. TSH, free 3,5,3 0 -L-triiodothyronine, free thyroxine, vitamin D, parathyroid hormone and bone turnover marker concentrations, and BMD measurements were available in all OPUS participants. Results: No coding sequence or splice site mutations affecting THRA or DIO2 were identified. Conclusions: Mutations affecting THRA or DIO2 are not a common cause of high BMD in healthy euthyroid post-menopausal women.European Journal of Endocrinology (2014) 170, 637-644 IntroductionThyroid hormones (thyroxine (T 4 ) and 3,5,3 0 -L-triiodothyronine (T 3 )) are essential for skeletal development, post-natal growth, and bone maturation. In adults, thyroid hormones regulate bone turnover, and normal euthyroid status is required to maintain optimal bone mass and mineralisation (1). Accordingly, thyrotoxicosis is a well-established cause of osteoporosis, and hypothyroidism is associated with an increased risk of fracture (2).The thyroid gland secretes T 4 and T 3 in a ratio of about 15:1, but T 4 is a pro-hormone and must be converted to T 3 in the peripheral tissues (3). Conversion of T 4 to T 3 in target cells is catalysed by type 2 iodothyronine deiodinase (DIO2), and the activity of this enzyme regulates intracellular availability of T 3 . Two nuclear receptors, TRa and TRb, mediate T 3 action in the target cells, and their relative levels of expression vary between tissues. European Journal of Endocrinology Clinical StudyA Gogakos and others THRA and DIO2 in women with high bone density For example, TRa is expressed at high levels in bone and cartilage, whereas TRb predominates in the hypothalamus and pituitary, where it mediates feedback control of the hypothalamic-pituitary-thyroid (HPT) axis (4). The syndrome of resistance to thyroid hormone (RTH) was described in 1967 (5) and the first THRB mutations affecting TRb were identified in 1989 (6). Heterozygous mutations of THRA were finally reported in three families in 2012 and 2013 (7, 8, 9, 10). Affected individuals a...

show abstract

High-Density Association Study of 383 Candidate Genes for Volumetric BMD at the Femoral Neck and Lumbar Spine Among Older Men

Cited by 59 publications

References 78 publications

SOST Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women With Osteoporosis

SOST Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women With Osteoporosis

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

THRA and DIO2 mutations are unlikely to be a common cause of increased bone mineral density in euthyroid post-menopausal women

Contact Info

Product

Resources

About