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CA repeat polymorphism of the TNFR2 gene is not associated with bone mineral density in two independent Caucasian populations

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Abstract

Osteoporosis has a strong genetic component, but the genes involved are poorly defined. Genome-wide scans in multiple populations have identified chromosome 1p36 as one region linked to bone mineral density (BMD). The tumor necrosis factor receptor 2 (TNFR2) at 1p36 is a positional and functional candidate gene in osteoporosis. In this study, we conducted linkage and association tests between the CA repeat polymorphism of the TNFR2 gene and BMD in two large independent samples using the quantitative transmission disequilibrium test (QTDT) program. The first group of subjects was composed of 1836 individuals from 79 multigeneration pedigrees. The second group was a randomly ascertained set of 636 individuals from 157 nuclear families. We found no evidence of association or linkage for spine or hip BMD in the samples of the multigenerational pedigrees or nuclear families. Through testing for association and for linkage, our data do not support the TNFR2 gene as a QTL underlying hip or spine BMD variation in our Caucasian populations.

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References

  1. J Dequeker J Nijs A Verstraeten P Geusens G Gevers (1987) ArticleTitleGenetic determinants of bone mineral content at the spine and radius: a twin study Bone 8 207–209 Occurrence Handle10.1016/8756-3282(87)90166-9 Occurrence Handle1:STN:280:BieC1czotFY%3D Occurrence Handle3446256

    Article  CAS  PubMed  Google Scholar 

  2. SW Slemeda JCC Christian CJ Williams JA Norton JCC Johnston (1991) ArticleTitleGenetic determinants of bone mass in adult woman: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates J Bone Miner Res 6 561–567

    Google Scholar 

  3. R Gueguen P Jouanny F Guillemin C Kuntz J Pourel G Siest (1995) ArticleTitleSegregation analysis and variance components analysis of bone mineral density in health families J Bone Miner Res 10 2017–2022 Occurrence Handle1:STN:280:BymC1M3nt1A%3D Occurrence Handle8619384

    CAS  PubMed  Google Scholar 

  4. HW Deng MR Stegman M Davies T Conway RR Recker (1999) ArticleTitleGenetic determination of peak bone mass (PBM) at hip and spine and common familiar environmental effects on bone qualities J Clin Densitom 2 251–263 Occurrence Handle10.1385/JCD:2:3:251 Occurrence Handle1:STN:280:DC%2BD3c%2FhvVCktQ%3D%3D Occurrence Handle10548821

    Article  CAS  PubMed  Google Scholar 

  5. QY Huang RR Recker HW Deng (2003) ArticleTitleSearching for the osteoporosis gene(s) in the post-genome era: progress and challenge Osteoporos Int 14 701–715 Occurrence Handle10.1007/s00198-003-1445-9 Occurrence Handle12904838

    Article  PubMed  Google Scholar 

  6. NA Morrison JC Qi A Tokita PJ Kelly L Crofts TV Nguyen PN Sambrook JA Eisman (1994) ArticleTitlePrediction of bone density from vitamin D receptor alleles Nature 367 284–287 Occurrence Handle10.1038/367284a0 Occurrence Handle1:CAS:528:DyaK2cXhsFGjur8%3D Occurrence Handle8161378

    Article  CAS  PubMed  Google Scholar 

  7. NC Ho L Jia CC Driscoll EM Gutter CA Francomano (2000) ArticleTitleA skeletal gene database J Bone Miner Res 15 2095–2122 Occurrence Handle1:CAS:528:DC%2BD3cXnvVKlt7o%3D Occurrence Handle11092392

    CAS  PubMed  Google Scholar 

  8. AG Uitterlinden JPTM van Leeuwen HAP Pols (2001) Genetics and genomics of osteoporosis R Marcus D Feldman J Kelsey (Eds) Osteoporosis, vol 1 Academic Press New York 639–667

    Google Scholar 

  9. M Devoto K Shimoya J Caminis J Ott A Tenenhouse MP Whyte L Sereda S Hall E Considine CJ Williams G Tromp H Kuivaniemi L Ala Kokko DJ Prockop LD Spotila (1998) ArticleTitleFirst-stage autosomal genome screen in extended pedigrees suggests genes predisposing to low bone mineral density on chromosomes 1p, 2p and 4q Eur J Hum Genet 6 151–157 Occurrence Handle10.1038/sj.ejhg.5200169 Occurrence Handle1:CAS:528:DyaK1MXhsFGktbs%3D Occurrence Handle9781060

    Article  CAS  PubMed  Google Scholar 

  10. LD Spotila M Devoto J Caminis R Kosich J Korkko J Ott A Tenenhouse DJ Prockop (1998) ArticleTitleSuggested linkage of low bone mineral density to chromosome 1p36 is extended to a second cohort of sib pairs J Bone Miner Res 23 S277

    Google Scholar 

  11. M Devoto C Specchia HH Li J Caminis A Tenenhouse H Rodriguez LD Spotila (2001) ArticleTitleVariance component linkage analysis indicates a QTL for femoral neck bone mineral density on chromosome 1p36 Hum Mol Genet 10 2447–2452 Occurrence Handle10.1093/hmg/10.21.2447 Occurrence Handle1:CAS:528:DC%2BD3MXos1aqsbo%3D Occurrence Handle11689491

    Article  CAS  PubMed  Google Scholar 

  12. SG Wilson PW Reed A Bansal M Chiano M Lindersson M Langdown RL Prince D Thompson E Thompson M Bailey PW Kleyn P Sambrook MM Shi TD Spector (2003) ArticleTitleComparison of genome screens for two independent cohorts provides replication of suggestive linkage of bone mineral density to 3p21 and 1p36 Am J Hum Genet 72 144–155 Occurrence Handle10.1086/345819 Occurrence Handle1:CAS:528:DC%2BD3sXis1ygtQ%3D%3D Occurrence Handle12478480

    Article  CAS  PubMed  Google Scholar 

  13. BA Kaufman PS White T Steinbrueck H Donis-Keller GM Broudeur (1994) ArticleTitleLinkage mapping of the tumor necrosis factor receptor 2 (TNFR2) gene to 1p36.2 using the single-strand conformation polymorphism technique Hum Genet 94 418–422 Occurrence Handle10.1007/BF00201604 Occurrence Handle1:CAS:528:DyaK2MXitFGjurg%3D Occurrence Handle7927340

    Article  CAS  PubMed  Google Scholar 

  14. CP Beltinger PS White JM Maris EP Sulman SF Jensen D LePaslier BJ Stallard DV Goeddel FJ De Sauvage GM Broudeur (1996) ArticleTitlePhysical mapping and genomic structure of the human TNFR2 gene Genomics 35 94–100 Occurrence Handle10.1006/geno.1996.0327 Occurrence Handle1:CAS:528:DyaK28Xkt12qsLk%3D Occurrence Handle8661109

    Article  CAS  PubMed  Google Scholar 

  15. LD Spotila H Rodriguez M Koch K Adams J Caminis HS Tenenhouse A Tenenhouse (2000) ArticleTitleAssociation of a polymorphism in the TNFR2 gene with low bone mineral density J Bone Miner Res 15 1376–1383 Occurrence Handle1:CAS:528:DC%2BD3cXltFSiurk%3D Occurrence Handle10893687

    CAS  PubMed  Google Scholar 

  16. OM Albagha FEA McGuigan D Reid SH Ralston (1999) ArticleTitleAssociation mapping of a locus for regulation of bone mass in the normal population using DNA pooling J Bone Miner Res 14 S142

    Google Scholar 

  17. OM Albagha PN Tasker FEA McGuigan D Reid SH Ralston (2002) ArticleTitleLinkage disequilibrium between polymorphisms in the human TNFRSF1B gene and their association with bone mass in perimenopausal women Hum Mol Genet 11 2289–2295 Occurrence Handle10.1093/hmg/11.19.2289 Occurrence Handle1:CAS:528:DC%2BD38XmvValsrY%3D Occurrence Handle12217957

    Article  CAS  PubMed  Google Scholar 

  18. LD Spotila H Rodriguez M Koch HS Tenenhouse A Tenenhouse H Li M Devoto (2003) ArticleTitleAssociation analysis of bone mineral density and single nucleotide polymorphisms in two candidate genes on chromosome 1p36 Calcif Tissue Int 73 140–146 Occurrence Handle10.1007/s00223-002-2079-1 Occurrence Handle1:CAS:528:DC%2BD3sXntVWlurk%3D Occurrence Handle14565595

    Article  CAS  PubMed  Google Scholar 

  19. PN Tasker OME Albagha CB Masson DM Reid SH Ralston (2004) ArticleTitleAssociation between TNFRSF1B polymorphisms and bone mineral density, bone loss and fracture Osteoporos Int 15 903–908 Occurrence Handle10.1007/s00198-004-1617-2 Occurrence Handle1:CAS:528:DC%2BD2cXotlKnsL0%3D Occurrence Handle15071724

    Article  CAS  PubMed  Google Scholar 

  20. H Xu LJ Zhao SF Lei MX Li X Sun FY Deng DK Jiang HW Deng (2005) ArticleTitleThe (CA)n polymorphism of the TNFR2 gene is associated with peak bone density in Chinese nuclear families J Hum Genet 50 301–304 Occurrence Handle1:CAS:528:DC%2BD2MXnvVWqsb4%3D Occurrence Handle15886863

    CAS  PubMed  Google Scholar 

  21. Y Abu-Amer J Erdmann L Alexopoulou G Kollias FP Ross SL Teitelbaum (2000) ArticleTitleTumor necrosis factor receptor types 1 and 2 differentially regulate osteoclastogenesis J Biol Chem 275 27307–27310 Occurrence Handle1:CAS:528:DC%2BD3cXmsVWqtr8%3D Occurrence Handle10874036

    CAS  PubMed  Google Scholar 

  22. HW Deng FH Xu QY Huang H Shen HY Deng T Conway YJ Liu YZ Liu JL Li HT Zhang KM Davies RR Recker (2002) ArticleTitleA whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait loci for osteoporosis J Clin Endocrinol Metab 87 5151–5159 Occurrence Handle10.1210/jc.2002-020474 Occurrence Handle1:CAS:528:DC%2BD38Xos1ynt7s%3D Occurrence Handle12414886

    Article  CAS  PubMed  Google Scholar 

  23. JL Li HY Deng DB Lai F Xu J Chen G Gao RR Recker HW Deng (2001) ArticleTitleTowards high-throughput genotyping: a dynamic and automatic software for manipulating large-scale genotype data using fluorescently labeled dinucleotide markers Genome Res 11 1304–1314 Occurrence Handle10.1101/gr.159701 Occurrence Handle1:CAS:528:DC%2BD3MXltFaiur4%3D Occurrence Handle11435414

    Article  CAS  PubMed  Google Scholar 

  24. JR O'Connell DE Weeks (1998) ArticleTitlePedCheck: a program for identification of genotype incompatibilities in linkage analysis Am J Hum Genet 63 259–266 Occurrence Handle10.1086/301904 Occurrence Handle9634505

    Article  PubMed  Google Scholar 

  25. RR Recker J Lappe K Davies K Heaney (2000) ArticleTitleCharacterization of perimenopausal bone loss: a perspective study J Bone Miner Res 16 1965–1973

    Google Scholar 

  26. GR Abecasis LR Cardon WO Cookson (2000) ArticleTitleA general test of association for quantitative traits in nuclear families Am J Hum Genet 66 279–292 Occurrence Handle10.1086/302698 Occurrence Handle1:STN:280:DC%2BD3c7gtVKhuw%3D%3D Occurrence Handle10631157

    Article  CAS  PubMed  Google Scholar 

  27. GR Abecasis WO Cookson LR Cardon (2000) ArticleTitlePedigree tests of transmission disequilibirum Eur J Hum Genet 8 545–551 Occurrence Handle10.1038/sj.ejhg.5200494 Occurrence Handle1:STN:280:DC%2BD3M%2FgvVCjsw%3D%3D Occurrence Handle10909856

    Article  CAS  PubMed  Google Scholar 

  28. D Rabinowitz (1997) ArticleTitleA transmission disequilibrium test for quantitative trait loci Hum Hered 47 342–350 Occurrence Handle1:STN:280:DyaK1c%2Fltleitg%3D%3D Occurrence Handle9391826

    CAS  PubMed  Google Scholar 

  29. DW Fulker SS Cherny PC Sham JK Hewitt (1999) ArticleTitleCombined linkage and association sib-pair analysis for quantitative traits Am J Hum Genet 64 259–267 Occurrence Handle10.1086/302193 Occurrence Handle1:STN:280:DyaK1M7hsFWjsQ%3D%3D Occurrence Handle9915965

    Article  CAS  PubMed  Google Scholar 

  30. AV Benjafield XL Wang BJ Morris (2001) ArticleTitleTumor necrosis factor receptor 2 gene (TNFRSF1B) in genetic basis of coronary artery disease J Mol Med 79 109–115 Occurrence Handle10.1007/s001090000168 Occurrence Handle1:CAS:528:DC%2BD3MXjvVOiu7o%3D Occurrence Handle11357933

    Article  CAS  PubMed  Google Scholar 

  31. QY Huang FH Xu H Shen YJ Liu YZ Liu LZ Zhao H Deng T Conway JL Li KM Davies RR Recker HW Deng (2004) ArticleTitleThe second-stage genome scan for QTLs underlying BMD variation Calcif Tissue Int 75 138–143 Occurrence Handle10.1007/s00223-004-0088-y Occurrence Handle1:CAS:528:DC%2BD2cXnsFWls7w%3D Occurrence Handle15085314

    Article  CAS  PubMed  Google Scholar 

  32. N Risch H Zhang (1995) ArticleTitleExtreme discordant sib pairs for mapping quantitative trait loci in humans Science 268 1584–1589 Occurrence Handle1:CAS:528:DyaK2MXmtlarsbw%3D Occurrence Handle7777857

    CAS  PubMed  Google Scholar 

  33. M Miyao H Morita T Hosoi H Kurihara S Inoue S Hoshino M Shiraki Y Yazaki Y Ouchi (2000) ArticleTitleAssociation of methylenetetrahydrofolate reductase (MTHFR) polymorphism with bone mineral density in postmenopausal Japanese women Calcif Tissue Int 66 190–194 Occurrence Handle10.1007/s002230010038 Occurrence Handle1:CAS:528:DC%2BD3cXhslSiurw%3D Occurrence Handle10666493

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. College of Life Sciences, Central China Normal University, Hubei, China

    Qing-Yang Huang

  2. College of Life Sciences, Hunan Normal University, Hunan, China

    Hong-Wen Deng

  3. Key Laboratory of Biomedical Information Engineering of the Ministry of Education and the Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China

    Hong-Wen Deng

  4. Osteoporosis Research Center, Creighton University, 601 N. 30th St., Suite 6787, Omaha, NE, 68131, USA

    Qing-Yang Huang, Hui Shen, Hong-Yi Deng, Theresa Conway, Leo Elze, K. Michael Davies, Robert R. Recker & Hong-Wen Deng

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  1. Qing-Yang Huang
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  2. Hui Shen
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  3. Hong-Yi Deng
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  4. Theresa Conway
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  5. Leo Elze
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  6. K. Michael Davies
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  8. Hong-Wen Deng
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Correspondence to Hong-Wen Deng.

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Huang, QY., Shen, H., Deng, HY. et al. CA repeat polymorphism of the TNFR2 gene is not associated with bone mineral density in two independent Caucasian populations. J Bone Miner Metab 24, 132–137 (2006). https://doi.org/10.1007/s00774-005-0659-7

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  • DOI: https://doi.org/10.1007/s00774-005-0659-7

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