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No association between polymorphisms of proliferator-activated receptor-gamma gene and peak bone mineral density variation in Chinese nuclear families

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An Erratum to this article was published on 19 March 2010

Abstract

Summary

Association between SNPs in polymorphism in proliferator-activated receptor-gamma (PPARG) and peak bone mineral density (BMD) variation of women was measured in 401 Chinese nuclear families using quantitative transmission disequilibrium test (QTDT). The peak BMD variation was not attributable to PPARG in our sample.

Introduction

The purpose of this study is to test whether genetic PPARG might play a role in normal variation in peak BMD.

Methods

We genotyped 10 tagging SNPs in PPARG using allele-specific polymerase chain reaction and further test whether these SNPs were associated with peak BMD variation at the lumbar spine and femoral neck of women in 401 Chinese nuclear families using QTDT. Furthermore, the association between these SNPs in PPARG and BMD in 710 postmenopausal Chinese women was measured.

Results

Using QTDT for within-family association, we failed to find that single SNP and haplotype were significantly associated with peak BMD at the lumbar spine and femoral neck. Meanwhile, we found that only rs1801282 was significantly associated with BMD at the lumbar spine in postmenopausal women (P = 0.013).

Conclusions

Our present results suggest, for the first time, that the genetic polymorphism in PPARG is not a major contributor to the observed variability in peak BMD at the lumbar spine and femoral neck in Chinese women.

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References

  1. Brown LB, Streeten EA, Shapiro JR, McBride D, Shuldiner AR, Peyser PA, Mitchell BD (2005) Genetic and environmental influences on bone mineral density in pre- and post-menopausal women. Osteoporos Int 16:1849–1856

    Article  PubMed  Google Scholar 

  2. Peacock M, Koller DL, Hui S, Johnston CC, Foroud T, Econs MJ (2004) Peak bone mineral density at the hip is linked to chromosomes 14q and 15q. Osteoporos Int 15:489–496

    Article  PubMed  Google Scholar 

  3. Kelly PJ, Nguyen T, Hopper J, Pocock N, Sambrook P, Eisman J (1993) Change in axial bone mineral density with age: a twin study. J Bone Miner Res 8:11–17

    Article  CAS  PubMed  Google Scholar 

  4. Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79:1147–1156

    Article  CAS  PubMed  Google Scholar 

  5. Ackert-Bicknell C, Rosen C (2006) The genetics of PPARG and the skeleton. PPAR Res 2006:1–8

    Article  CAS  Google Scholar 

  6. Fajas L, Auboeuf D, Raspé E, Schoonjans K, Lefebvre AM, Saladin R, Najib J, Laville M, Fruchart JC, Deeb S, Vidal-Puig A, Flier J, Briggs MR, Staels B, Vidal H, Auwerx J (1997) The organization, promoter analysis, and expression of the human PPARγ. J Bio Chem 270:18779–18789

    Article  Google Scholar 

  7. Akune T, Ohba S, Kamekura S, Yamaguchi M, Chung UI, Kubota N, Terauchi Y, Harada Y, Azuma Y, Nakamura K, Kadowaki T, Kawaguchi H (2004) PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 113:846–855

    CAS  PubMed  Google Scholar 

  8. Pei L, Tontonoz P (2004) Fat’s loss is bone’ gain. J Clin Invest 113:805–806

    CAS  PubMed  Google Scholar 

  9. Schwartz AV, Sellmeyer DE, Vittinghoff E, Palermo L, Lecka-Czernik B, Feingold KR, Strotmeyer ES, Resnick HE, Carbone L, Beamer BA, Park SW, Lane NE, Harris TB, Cummings SR (2006) Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 91:3349–3354

    Article  CAS  PubMed  Google Scholar 

  10. Grey A (2008) Skeletal consequences of thiazolidinedione therapy. Osteoporos Int 19:129–137

    Article  CAS  PubMed  Google Scholar 

  11. Deeb SS, Fajas L, Nemoto M, Pihlajamäki J, Mykkänen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J (1998) A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 20:284–287

    Article  CAS  PubMed  Google Scholar 

  12. Jaziri R, Lobbens S, Aubert R, Péan F, Lahmidi S, Vaxillaire M, Porchay I, Bellili N, Tichet J, Balkau B, Froguel P, Marre M, Fumeron F, DESIR Study Group (2006) The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing hyperglycemia over 6 years and combines with the effect of the APM1 G-11391A single nucleotide polymorphism: the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Diabetes 55:1157–1162

    Article  CAS  PubMed  Google Scholar 

  13. Ogawa S, Urano T, Hosoi T, Miyao M, Hoshino S, Fujita M, Shiraki M, Orimo H, Ouchi Y, Inoue S (1999) Association of bone mineral density with a polymorphism of the peroxisome proliferator-activated receptor gamma gene: PPARgamma expression in osteoblasts. Biochem Biophys Res Commun 260:122–126

    Article  CAS  PubMed  Google Scholar 

  14. Rhee EJ, Oh KW, Lee WY, Kim SY, Oh ES, Baek KH, Kang MI, Kim SW (2005) The effects of C161-- > T polymorphisms in exon 6 of peroxisome proliferator-activated receptor-gamma gene on bone mineral metabolism and serum osteoprotegerin levels in healthy middle-aged women. Am J Obstet Gynecol 192:1087–1093

    Article  CAS  PubMed  Google Scholar 

  15. Casado-Díaz A, Cuenca-Acevedo R, Quesada JM, Dorado G (2007) Individual single tube genotyping and DNA pooling by allele-specific PCR to uncover associations of polymorphisms with complex diseases. Clin Chim Acta 376:155–162

    Article  PubMed  CAS  Google Scholar 

  16. Rhee EJ, Oh KW, Yun EJ, Jung CH, Park CY, Lee WY, Oh ES, Baek KH, Kang MI, Park SW, Kim SW (2007) The association of Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma gene with serum osteoprotegerin levels in healthy Korean women. Exp Mol Med 9:696–704

    Google Scholar 

  17. Ackert-Bicknell CL, Demissie S, de Evsikova CM, Hsu YH, Demambro VE, Karasik D, Cupples LA, Ordovas JM, Tucker KL, Cho K, Canalis E, Paigen B, Churchill GA, Forejt J, Beamer WG, Ferrari S, Bouxsein ML, Kiel DP, Rosen CJ (2008) A PPARG by dietary fat interaction influences bone mass in mice and humans. J Bone Miner Res 23:1398–1408

    Article  PubMed  Google Scholar 

  18. Qin YJ, Shen H, Huang QR, Zhao LJ, Zhou Q, Li MX, He JW, Mo XY, Lu JH, Recker RR, Deng HW (2003) Estrogen receptor alpha gene polymorphisms and peak bone density in Chinese nuclear families. J Bone Miner Res 18:1028–1035

    Article  CAS  PubMed  Google Scholar 

  19. Zhang ZL, He JW, Qin YJ, Hu YQ, Li M, Zhang H, Hu WW, Liu YJ, Gu JM (2008) Association between myostatin gene polymorphisms and peak BMD variation in Chinese nuclear families. Osteoporos Int 19:39–47

    Article  CAS  PubMed  Google Scholar 

  20. Zhang ZL, Qin YJ, Huang QR, Hu YQ, Li M, He JW, Zhang H, Liu YJ, Hu WW (2006) Bone mineral density of the spine and femur in healthy Chinese men. Asian J Androl 8:419–427

    Article  PubMed  Google Scholar 

  21. Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989

    Article  CAS  PubMed  Google Scholar 

  22. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  CAS  PubMed  Google Scholar 

  23. Zhang ZL, He JW, Qin YJ, Hu YQ, Li M, Liu YJ, Zhang H, Hu WW (2007) Association between SNP and haplotypes in PPARGC1 and adiponectin genes and bone mineral density in Chinese nuclear families. Acta Pharmacol Sin 28:287–295

    Article  CAS  PubMed  Google Scholar 

  24. McIntyre LM, Martin ER, Simonsen KL, Kaplan NL (2000) Circumventing multiple testing: a multilocus Monte Carlo approach to testing for association. Genet Epidemiol 19:18–29

    Article  CAS  PubMed  Google Scholar 

  25. Kim K, Lee S, Rudy J, Valentine RJ (2007) Association of Pro12Ala polymprphism in the peroxisome proliferator-activated receptor γ2 gene with obesity and hypertension in Korean women. J Nutr Sci Vitaminol 53:239–246

    Article  CAS  PubMed  Google Scholar 

  26. Mori H, Ikegami H, Kawaguchi Y, Seino S, Yokoi N, Takeda J, Inoue I, Seino Y, Yasuda K, Hanafusa T, Yamagata K, Awata T, Kadowaki T, Hara K, Yamada N, Gotoda T, Iwasaki N, Iwamoto Y, Sanke T, Nanjo K, Oka Y, Matsutani A, Maeda E, Kasuga M (2001) The Pro12 -- > Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes 50:891–894

    Article  CAS  PubMed  Google Scholar 

  27. Abecasis GR, Cardon LR, Cookson WO (2005) A general test of association for quantitative traits in nuclear families. Am J Hum Genet 66:279–292

    Article  Google Scholar 

  28. Liu XH, Liu YJ, Jiang DK, Li YM, Li MX, Qin YJ, Jian WX, Zhou Q, Deng HW (2003) No evidence for linkage and/or association of human alpha2-HS glycoprotein gene with bone mineral density variation in Chinese nuclear families. Calcif Tissue Int 73:244–250

    Article  CAS  PubMed  Google Scholar 

  29. Deng FY, Liu MY, Li MX, Lei SF, Qin YJ, Zhou Q, Liu YJ, Deng HW (2003) Tests of linkage and association of the COL1A2 gene with bone phenotypes' variation in Chinese nuclear families. Bone 33:614–619

    Article  CAS  PubMed  Google Scholar 

  30. Masud S, Ye S (2003) Effect of the peroxisome proliferator-activated receptor γ gene Pro12Ala variant on body mass index: a meta-analysis. J Med Genet 40:773–780

    Article  CAS  PubMed  Google Scholar 

  31. Vaccaro O, Lapice E, Monticelli A, Giacchetti M, Castaldo I, Galasso R, Pinelli M, Donnarumma G, Rivellese AA, Cocozza S, Riccardi G (2007) Pro12Ala polymorphism of the PPARgamma2 locus modulates the relationship between energy intake and body weight in type 2 diabetic patients. Diabetes Care 30:1156–1161

    Article  CAS  PubMed  Google Scholar 

  32. Yamamoto Y, Hirose H, Miyashita K, Nishikai K, Saito I, Taniyama M, Tomita M, Saruta T (2002) PPAR(gamma)2 gene Pro12Ala polymorphism may influence serum level of an adipocyte-derived protein, adiponectin, in the Japanese population. Metabolism 51:1407–1409

    Article  CAS  PubMed  Google Scholar 

  33. Peacock M, Koller DL, Fishburn T, Krishnan S, Lai D, Hui S, Johnston CC, Foroud T, Econs MJ (2005) Sex-specific and non-sex-specific quantitative trait loci contribute to normal variation in bone mineral density in men. J Clin Endocrinol Metab 90:3060–3066

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The study was supported by the National Natural Science Foundation of China (nos. 30570891, 30771019) and Program of Shanghai subject chief scientist (no. 08XD1403000). We wish to thank anonymous reviewers for comments that improve our manuscript.

Conflicts of interest

None.

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Authors and Affiliations

  1. The Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 600 Yi-Shan Rd, Shanghai, 200233, People’s Republic of China

    H. Yue, J.-W. He, H. Zhang, W.-W. Hu, Y.-Q. Hu, M. Li, Y.-J. Liu & Z.-L. Zhang

  2. The Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory Mellitus, Shanghai, People’s Republic of China

    H. Yue & S.-H. Wu

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  1. H. Yue
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Correspondence to Z.-L. Zhang.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00198-010-1196-3

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Yue, H., He, JW., Zhang, H. et al. No association between polymorphisms of proliferator-activated receptor-gamma gene and peak bone mineral density variation in Chinese nuclear families. Osteoporos Int 21, 873–882 (2010). https://doi.org/10.1007/s00198-009-1028-5

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  • DOI: https://doi.org/10.1007/s00198-009-1028-5

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