Transforming Growth Factor Beta-1 (TGFB1) and Peak Bone Mass: Association Between Intragenic Polymorphisms and Quantitative Ultrasound of the Heel

Overview

Journal BMC Musculoskelet Disord

Publisher Biomed Central

Specialties Orthopedics
Physiology

Date 2005 Jun 16

PMID 15955247

Citations 11

Authors

Peter Tzakas

Betty Y L Wong

Alexander G Logan

Laurence A Rubin

David E C Cole

Affiliations

Soon will be listed here.

Abstract

Background: Variance of peak bone mass has a substantial genetic component, as has been shown with twin studies examining quantitative measures such as bone mineral density (BMD) and quantitative ultrasound (QUS). Evidence implicating single nucleotide polymorphisms (SNPs) of the transforming growth factor beta-1 (TGFB1) gene is steadily accumulating. However, a comprehensive look at multiple SNPs at this locus for their association with indices of peak bone mass has not been reported.

Methods: A cohort of 653 healthy Caucasian females 18 to 35 years old was genotyped for seven TGFB1 SNPs. Polymorphisms were detected by restriction endonuclease digestion of amplified DNA segments.

Results: The frequencies of the least common allele at G-800A, C-509T, codon 10 (L10P), codon 25 (R25P), codon 263 (T263I), C861-20T, and 713-8 delC loci were 0.07, 0.33, 0.41, 0.08, 0.04, 0.25 and 0.01, respectively. A significant association was seen between QUS Stiffness Index (QUS-SI) and the SNP at codon 10 and the linked promoter SNP, C-509T. This association remained significant after multiple regression was used to incorporate important clinical covariates--age, BMI, level of activity, family history, and caffeine intake--into the model.

Conclusion: The association of QUS-SI with -509T is consistent with a gene-dose effect, while only individuals homozygous for the codon 10P allele showed a significant increase. In this cohort of young healthy Caucasian females, the T allele at position -509 is associated with greater bone mass as measured by calcaneal ultrasound.

Citing Articles

Association of and Gene Polymorphisms with Osteoporosis in a Study of Taiwanese Osteoporotic Patients.

Tu M, Han K, Lan Y, Chang K, Lai C, Staniczek T Genes (Basel). 2021; 12(6).

PMID: 34207210 PMC: 8233820. DOI: 10.3390/genes12060930.

Genetic markers of osteoarthritis: early diagnosis in susceptible Pakistani population.

Badshah Y, Shabbir M, Hayat H, Fatima Z, Burki A, Khan S J Orthop Surg Res. 2021; 16(1):124.

PMID: 33563308 PMC: 7871631. DOI: 10.1186/s13018-021-02230-x.

Significant Improvement of Clinical Symptoms, Bone Lesions, and Bone Turnover after Long-Term Zoledronic Acid Treatment in Patients with a Severe Form of Camurati-Engelmann Disease.

Baroncelli G, Ferretti E, Pini C, Toschi B, Consolini R, Bertelloni S Mol Syndromol. 2017; 8(6):294-302.

PMID: 29230158 PMC: 5701277. DOI: 10.1159/000479859.

Association between transforming growth factor-beta 1 gene single nucleotide polymorphisms and knee osteoarthritis susceptibility in a Chinese Han population.

Lu N, Lu J, Zhou C, Zhong F J Int Med Res. 2017; 45(5):1495-1504.

PMID: 28627979 PMC: 5718715. DOI: 10.1177/0300060517705719.

Identification of transcriptional factors and key genes in primary osteoporosis by DNA microarray.

Xie W, Ji L, Zhao T, Gao P Med Sci Monit. 2015; 21:1333-44.

PMID: 25957414 PMC: 4436946. DOI: 10.12659/MSM.894111.

References

Patel M, Cole D, Smith J, Hawker G, Wong B, Trang H . Alleles of the estrogen receptor alpha-gene and an estrogen receptor cotranscriptional activator gene, amplified in breast cancer-1 (AIB1), are associated with quantitative calcaneal ultrasound. J Bone Miner Res. 2000; 15(11):2231-9. DOI: 10.1359/jbmr.2000.15.11.2231. View

Janssens K, Gershoni-Baruch R, Guanabens N, Migone N, Ralston S, Bonduelle M . Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease. Nat Genet. 2000; 26(3):273-5. DOI: 10.1038/81563. View

Yamada Y, Miyauchi A, Takagi Y, Tanaka M, Mizuno M, Harada A . Association of the C-509-->T polymorphism, alone of in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. J Mol Med (Berl). 2001; 79(2-3):149-56. DOI: 10.1007/s001090100190. View

Yamada Y . Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis. Pharmacogenetics. 2001; 11(9):765-71. DOI: 10.1097/00008571-200112000-00004. View

Hinke V, Seck T, Clanget C, Scheidt-Nave C, Ziegler R, Pfeilschifter J . Association of transforming growth factor-beta1 (TGFbeta1) T29 --> C gene polymorphism with bone mineral density (BMD), changes in BMD, and serum concentrations of TGF-beta1 in a population-based sample of postmenopausal german women. Calcif Tissue Int. 2002; 69(6):315-20. DOI: 10.1007/s002230020024. View

Cohen Jr M . TGF beta/Smad signaling system and its pathologic correlates. Am J Med Genet A. 2002; 116A(1):1-10. DOI: 10.1002/ajmg.a.10750. View

Ziv E, Kahn A, Cauley J, Morin P, Saiz R, Browner W . No association between the TGF-beta 1 Leu10Pro polymorphism and osteoporosis among white women in the United States. Am J Med. 2003; 114(3):227-31. DOI: 10.1016/s0002-9343(02)01393-1. View

Langdahl B, Carstens M, Stenkjaer L, Eriksen E . Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis. Bone. 2003; 32(3):297-310. DOI: 10.1016/s8756-3282(02)00971-7. View

Dick I, Devine A, Li S, Dhaliwal S, Prince R . The T869C TGF beta polymorphism is associated with fracture, bone mineral density, and calcaneal quantitative ultrasound in elderly women. Bone. 2003; 33(3):335-41. DOI: 10.1016/s8756-3282(03)00158-3. View

10.

Kinoshita A, Fukumaki Y, Shirahama S, Miyahara A, Nishimura G, Haga N . TGFB1 mutations in four new families with Camurati-Engelmann disease: confirmation of independently arising LAP-domain-specific mutations. Am J Med Genet A. 2004; 127A(1):104-107. DOI: 10.1002/ajmg.a.20671. View

11.

Hamilton D, Cole D . Standardizing a composite measure of linkage disequilibrium. Ann Hum Genet. 2004; 68(Pt 3):234-9. DOI: 10.1046/j.1529-8817.2004.00056.x. View

12.

Lau H, Ho A, Luk K, Kung A . Transforming growth factor-beta1 gene polymorphisms and bone turnover, bone mineral density and fracture risk in southern Chinese women. Calcif Tissue Int. 2004; 74(6):516-21. DOI: 10.1007/s00223-004-0163-4. View

13.

Derynck R, Jarrett J, Chen E, Goeddel D . The murine transforming growth factor-beta precursor. J Biol Chem. 1986; 261(10):4377-9. View

14.

Seyedin S, Thompson A, BENTZ H, Rosen D, McPherson J, Conti A . Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta. J Biol Chem. 1986; 261(13):5693-5. View

15.

Pocock N, Eisman J, Hopper J, Yeates M, Sambrook P, Eberl S . Genetic determinants of bone mass in adults. A twin study. J Clin Invest. 1987; 80(3):706-10. PMC: 442294. DOI: 10.1172/JCI113125. View

16.

Pfeilschifter J, Seyedin S, Mundy G . Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures. J Clin Invest. 1988; 82(2):680-5. PMC: 303563. DOI: 10.1172/JCI113647. View

17.

Antosz M, Bellows C, Aubin J . Effects of transforming growth factor beta and epidermal growth factor on cell proliferation and the formation of bone nodules in isolated fetal rat calvaria cells. J Cell Physiol. 1989; 140(2):386-95. DOI: 10.1002/jcp.1041400225. View

18.

Sawitzke A, Sawitzke A, Ward R . HLA-DPB typing using co-digestion of amplified fragments allows efficient identification of heterozygous genotypes. Tissue Antigens. 1992; 40(4):175-81. DOI: 10.1111/j.1399-0039.1992.tb02042.x. View

19.

Morrison N, Qi J, Tokita A, Kelly P, Crofts L, Nguyen T . Prediction of bone density from vitamin D receptor alleles. Nature. 1994; 367(6460):284-7. DOI: 10.1038/367284a0. View

20.

Dieudonne S, Semeins C, Goei S, Vukicevic S, Nulend J, Sampath T . Opposite effects of osteogenic protein and transforming growth factor beta on chondrogenesis in cultured long bone rudiments. J Bone Miner Res. 1994; 9(6):771-80. DOI: 10.1002/jbmr.5650090603. View