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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2016

Open Access 01-12-2016 | Research article

The TGFB1 gene is associated with curve severity but not with the development of adolescent idiopathic scoliosis: a replication study in the Chinese population

Authors: Leilei Xu, Weixiang Sun, Xiaodong Qin, Yong Qiu, Zezhang Zhu

Published in: BMC Musculoskeletal Disorders | Issue 1/2016

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Abstract

Background

The transforming growth factor beta-1 (TGFB1) gene was recently reported to be a new susceptible gene of adolescent idiopathic scoliosis (AIS) in Russian population. This study aimed to replicate the relationship between the TGFB1 gene and the susceptibility of AIS in a Chinese population, and to further describe its association with the curve severity.

Methods

A total of 1251 female AIS patients and 994 age-matched healthy controls were included in this study. The rs1800469 of TGFB1 gene was genotyped for all participants using the PCR-based Invader assay. The differences of genotype and allele distributions between AIS patients and healthy controls were assessed using the Chi-square test. One-way ANOVA test was used to compare the mean Cobb angles among patients with different genotypes.

Results

There was no significant difference in terms of the genotype and the allele frequency between the patients and the controls. The mean Cobb angle was 34.7 ± 11.9° (range 25–61°). Case-only analysis showed that rs1800469 was significantly associated with the curve severity. Patients with genotype TT had remarkably higher curve magnitude (39.1 ± 12.8°) than those with genotype CT (34.8 ± 11.1°) or CC (32.1 ± 10.6°).

Conclusions

The TGFB1 gene may not be a predisposition gene of AIS in the Chinese population. However, it can play a role in the curve progression of AIS. Replication studies in other ethnic groups are warranted to understand the implication of TGFB1 gene in AIS.
Literature
1.
Weinstein SL. Advances in the diagnosis and management of adolescent idiopathic scoliosis. J Pediatr Orthop. 1994;14:561–3.CrossRefPubMed
2.
Lonstein JE. Adolescent idiopathic scoliosis: screening and diagnosis. Instr Course Lect. 1989;38:105–13.PubMed
3.
Horne JP, Flannery R, Usman S. Adolescent idiopathic scoliosis: diagnosis and management. Am Fam Physician. 2014;89:193–8.PubMed
4.
Burwell RG, Aujla RK, Kirby AS, Dangerfield PH, Moulton A, Cole AA, et al. Body mass index of girls in health influences menarche and skeletal maturation: a leptin-sympathetic nervous system focus on the trunk with hypothalamic asymmetric dysfunction in the pathogenesis of adolescent idiopathic scoliosis? Stud Health Technol Inform. 2008;140:9–21.PubMed
5.
Girardo M, Bettini N, Dema E, Cervellati S. The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis (AIS). Eur Spine J. 2011;20 Suppl 1:S68–74.CrossRefPubMed
6.
Burwell RG, Dangerfield PH. Pathogenesis of progressive adolescent idiopathic scoliosis. Platelet activation and vascular biology in immature vertebrae: an alternative molecular hypothesis. Acta Orthop Belg. 2006;72:247–60.PubMed
7.
Ahn UM, Ahn NU, Nallamshetty L, Buchowski JM, Rose PS, Miller NH, et al. The etiology of adolescent idiopathic scoliosis. Am J Orthop (Belle Mead NJ). 2002;31:387–95.
8.
Miller NH. Cause and natural history of adolescent idiopathic scoliosis. Orthop Clin North Am. 1999;30:343–52.CrossRefPubMed
9.
Miller NH, Mims B, Child A, Milewicz DM, Sponseller P, Blanton SH. Genetic analysis of structural elastic fiber and collagen genes in familial adolescent idiopathic scoliosis. J Orthop Res. 1996;14:994–9.CrossRefPubMed
10.
Gurnett CA, Alaee F, Bowcock A, Kruse L, Lenke LG, Bridwell KH, et al. Genetic linkage localizes an adolescent idiopathic scoliosis and pectus excavatum gene to chromosome 18 q. Spine (Phila Pa 1976). 2009;34:E94–100.CrossRef
11.
Gao X, Gordon D, Zhang D, Browne R, Helms C, Gillum J, et al. CHD7 gene polymorphisms are associated with susceptibility to idiopathic scoliosis. Am J Hum Genet. 2007;80:957–65.CrossRefPubMedPubMedCentral
12.
Miller NH, Justice CM, Marosy B, Doheny KF, Pugh E, Zhang J, et al. Identification of candidate regions for familial idiopathic scoliosis. Spine (Phila Pa 1976). 2005;30:1181–7.CrossRef
13.
Wu J, Qiu Y, Zhang L, Sun Q, Qiu X, He Y. Association of estrogen receptor gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2006;31:1131–6.CrossRef
14.
Inoue M, Minami S, Nakata Y, Kitahara H, Otsuka Y, Isobe K, et al. Association between estrogen receptor gene polymorphisms and curve severity of idiopathic scoliosis. Spine (Phila Pa 1976). 2002;27:2357–62.CrossRef
15.
Zhang HQ, Lu SJ, Tang MX, Chen LQ, Liu SH, Guo CF, et al. Association of estrogen receptor beta gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2009;34:760–4.CrossRef
16.
Chen Z, Tang NL, Cao X, Qiao D, Yi L, Cheng JC, et al. Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population. Eur J Hum Genet. 2009;17:525–32.CrossRefPubMed
17.
Qiu XS, Tang NL, Yeung HY, Lee KM, Hung VW, Ng BK, et al. Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2007;32:1748–53.CrossRef
18.
Wang H, Wu Z, Zhuang Q, Fei Q, Zhang J, Liu Y, et al. Association study of tryptophan hydroxylase 1 and arylalkylamine N-acetyltransferase polymorphisms with adolescent idiopathic scoliosis in Han Chinese. Spine (Phila Pa 1976). 2008;33:2199–203.CrossRef
19.
Nikolova S, Dikova M, Dikov D, Djerov A, Dzhebir G, Atanasov V, et al. Role of the IL-6 gene in the etiopathogenesis of idiopathic scoliosis. Anal Cell Pathol (Amst). 2015;2015:621893.
20.
Aulisa L, Papaleo P, Pola E, Angelini F, Aulisa AG, Tamburrelli FC, et al. Association between IL-6 and MMP-3 gene polymorphisms and adolescent idiopathic scoliosis: a case-control study. Spine (Phila Pa 1976). 2007;32:2700–2.CrossRef
21.
Mao S, Xu L, Zhu Z, Qian B, Qiao J, Yi L, et al. Association between genetic determinants of peak height velocity during puberty and predisposition to adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2013;38(12):1034–9.CrossRef
22.
Sharma S, Gao X, Londono D, Devroy SE, Mauldin KN, Frankel JT, et al. Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet. 2011;20:1456–66.CrossRefPubMedPubMedCentral
23.
Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N, et al. A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet. 2011;43:1237–40.CrossRefPubMed
24.
Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J, et al. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet. 2013;45:676–9.CrossRefPubMed
25.
Grauers A, Wang J, Einarsdottir E, Simony A, Danielsson A, Akesson K, et al. Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis. Spine J. 2015;15:2239–46.CrossRefPubMed
26.
Qiu XS, Lv F, Zhu ZZ, Qian BP, Wang B, Yu Y, et al. Lack of association between the CHL1 gene and adolescent idiopathic scoliosis susceptibility in Han Chinese: a case-control study. BMC Musculoskelet Disord. 2014;15:38.CrossRefPubMedPubMedCentral
27.
Nikolova S, Yablanski V, Vlaev E, Stokov L, Savov AS, Kremensky IM. Association between ESR1 common genetic polymorphisms and curve severity of idiopathic scoliosis in Bulgarian patients: A case-control study. C R Acad Bulg Sci. 2015;68:783–8.
28.
Nikolova S, Yablanski V, Vlaev E, Getova G, Atanasov V, Stokov L, et al. Alpha gene polymorphisms and susceptibility to idiopathic scoliosis in Bulgarian patients: a Case-control Study. OA Maced J Med Sci. 2015;3:278–82.CrossRef
29.
Tang NL, Yeung HY, Lee KM, Hung VW, Cheung CS, Ng BK, et al. A relook into the association of the estrogen receptor [alpha] gene (PvuII, XbaI) and adolescent idiopathic scoliosis: a study of 540 Chinese cases. Spine (Phila Pa 1976). 2006;31:2463–8.CrossRef
30.
Takahashi Y, Matsumoto M, Karasugi T, Watanabe K, Chiba K, Kawakami N, et al. Replication study of the association between adolescent idiopathic scoliosis and two estrogen receptor genes. J Orthop Res. 2011;29:834–7.CrossRefPubMed
31.
Janusz P, Kotwicki T, Andrusiewicz M, Kotwicka M. XbaI and PvuII polymorphisms of estrogen receptor 1 gene in females with idiopathic scoliosis: no association with occurrence or clinical form. PLoS One. 2013;8:e76806.CrossRefPubMedPubMedCentral
32.
Takahashi Y, Matsumoto M, Karasugi T, Watanabe K, Chiba K, Kawakami N, et al. Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese population. J Orthop Res. 2011;29:1055–8.CrossRefPubMed
33.
Ryzhkov II, Borzilov EE, Churnosov MP, Ataman AP, Dedkov AA, Polonikov AP. Transforming Growth Factor Beta 1 is a Novel Susceptibility Gene for Adolescent Idiopathic Scoliosis. Spine (Phila Pa 1976). 2013;12:E699–704.CrossRef
34.
Rienhoff HJ, Yeo CY, Morissette R, Khrebtukova I, Melnick J, Luo S, et al. A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis and clinical features overlapping with Marfan and Loeys-Dietz syndrome. Am J Med Genet A. 2013;161A:2040–6.CrossRefPubMed
35.
Kuechler A, Altmuller J, Nurnberg P, Kotthoff S, Kubisch C, Borck G. Exome sequencing identifies a novel heterozygous TGFB3 mutation in a disorder overlapping with Marfan and Loeys-Dietz syndrome. Mol Cell Probes. 2015. doi:10.​1016/​j.​mcp.​2015.​07.​003.PubMed
36.
Ingman WV, Robertson SA. The essential roles of TGFB1 in reproduction. Cytokine Growth Factor Rev. 2009;20:233–9.CrossRefPubMed
37.
Qiu GX, Guo SJ, Liu Y, Qian WW, Wu ZH. The expression of collagen type I, II and TGF-beta1 in the articular processes of scoliosis patients. Zhonghua Yi Xue Za Zhi. 2005;85:2391–4.PubMed
38.
Nerlich AG, Bachmeier BE, Boos N. Expression of fibronectin and TGF-beta1 mRNA and protein suggest altered regulation of extracellular matrix in degenerated disc tissue. Eur Spine J. 2005;14:17–26.CrossRefPubMed
39.
Jiang H, Qiu X, Dai J, Yan H, Zhu Z, Qian B, et al. Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis susceptibility in a Han Chinese population. Eur Spine J. 2013;22:282–6.CrossRefPubMed
40.
Fan YH, Song YQ, Chan D, Takahashi Y, Ikegawa S, Matsumoto M, et al. SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese. J Hum Genet. 2012;57:244–6.CrossRefPubMed
41.
Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999;8:93–7.CrossRefPubMed
42.
Silverman ES, Palmer LJ, Subramaniam V, Hallock A, Mathew S, Vallone J, et al. Transforming growth factor-beta1 promoter polymorphism C-509 T is associated with asthma. Am J Respir Crit Care Med. 2004;169:214–9.CrossRefPubMed
43.
Xu H, Qiu G, Wu Z, Wang Y, Zhang J, Liu Y, et al. Expression of transforming growth factor and basic fibroblast growth factor and core protein of proteoglycan in human vertebral cartilaginous endplate of adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2005;30:1973–8.CrossRef
Metadata
Title
The TGFB1 gene is associated with curve severity but not with the development of adolescent idiopathic scoliosis: a replication study in the Chinese population
Authors
Leilei Xu
Weixiang Sun
Xiaodong Qin
Yong Qiu
Zezhang Zhu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2016
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-016-0863-8

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