Top

European Spine Journal

Published in:

01-02-2018 | Original Article

Quantitative evaluation of the relationship between COMP promoter methylation and the susceptibility and curve progression of adolescent idiopathic scoliosis

Authors: Sai-hu Mao, Bang-ping Qian, Benlong Shi, Ze-zhang Zhu, Yong Qiu

Published in: European Spine Journal | Issue 2/2018

Abstract

Purpose

The cartilage oligomeric matrix protein (COMP) was reported to be down-regulated in adolescent idiopathic scoliosis (AIS). The purposes of the study were to evaluate the roles of COMP promoter methylation on the abnormal gene expression and the epigenetic phenotype in AIS.

Methods

DNA samples of 50 AIS patients and 50 healthy controls were analyzed. Five CpG sites of COMP gene were amplified and sequenced using the polymerase chain reaction (PCR) and the pyrophosphate sequencing technology, while the COMP gene expression was evaluated using real-time PCR. Comparisons were analyzed with the Chi-square test and independent t test. Pearson coefficients of correlation were used to evaluate the association between gene methylation and clinical phenotypes.

Results

The average COMP gene promoter methylation of the AIS and control groups was 12.26 ± 2.36 and 8.76 ± 1.94 (p < 0.0001), and correspondingly the relative expression of COMP gene expression was 0.52 ± 0.12 and 1.16 ± 0.52 (p < 0.001), respectively. The correlation analysis showed significantly negative correlation between methylation level and gene expression (p < 0.0001). The comparison analysis between AIS patients with positive and negative methylation showed significant difference in chronological age (p < 0.001) and Cobb angle of main curve (p = 0.011). The methylation level of the COMP promoters was significantly correlated with Cobb angle of main curve and age (p < 0.0001) among the five CpG sites.

Conclusions

AIS patients had significantly high COMP promoter methylation and low gene expression. Positive and high COMP promoter methylation was correlated with young age and high Cobb angle of main curve. Therefore, COMP gene promoter methylation may provide significant prognostic information in predicting the susceptibility and curve progression of AIS.

Weinstein SL, Dolan LA, Cheng JC, Danielsson A, Morcuende JA (2008) Adolescent idiopathic scoliosis. Lancet 371:1527–1537. doi:10.1016/s0140-6736(08)60658-3 CrossRefPubMed

Weinstein SL, Dolan LA, Wright JG, Dobbs MB (2013) Effects of bracing in adolescents with idiopathic scoliosis. N Engl J Med 369:1512–1521. doi:10.1056/NEJMoa1307337 CrossRefPubMedPubMedCentral

Zhu Z, Tang NL, Xu L, Qin X, Mao S, Song Y, Liu L, Li F, Liu P, Yi L, Chang J, Jiang L, Ng BK, Shi B, Zhang W, Qiao J, Sun X, Qiu X, Wang Z, Wang F, Xie D, Chen L, Chen Z, Jin M, Han X, Hu Z, Zhang Z, Liu Z, Zhu F, Qian BP, Yu Y, Wang B, Lee KM, Lee WY, Lam TP, Qiu Y, Cheng JC (2015) Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls. Nat Commun 6:8355. doi:10.1038/ncomms9355 CrossRefPubMedPubMedCentral

Qiu XS, Tang NL, Yeung HY, Lee KM, Hung VW, Ng BK, Ma SL, Kwok RH, Qin L, Qiu Y, Cheng JC (2007) Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine 32:1748–1753. doi:10.1097/BRS.0b013e3180b9f0ff CrossRefPubMed

Xu L, Qiu X, Sun X, Mao S, Liu Z, Qiao J, Qiu Y (2011) Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis. Eur Spine J 20:1757–1764. doi:10.1007/s00586-011-1874-7 CrossRefPubMedPubMedCentral

Wu J, Qiu Y, Zhang L, Sun Q, Qiu X, He Y (2006) Association of estrogen receptor gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine 31:1131–1136. doi:10.1097/01.brs.0000216603.91330.6f CrossRefPubMed

Inoue M, Minami S, Nakata Y, Kitahara H, Otsuka Y, Isobe K, Takaso M, Tokunaga M, Nishikawa S, Maruta T, Moriya H (2002) Association between estrogen receptor gene polymorphisms and curve severity of idiopathic scoliosis. Spine 27:2357–2362. doi:10.1097/01.brs.0000030305.30361.27 CrossRefPubMed

Chen Z, Tang NL, Cao X, Qiao D, Yi L, Cheng JC, Qiu Y (2009) Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population. Eur J Hum Genet EJHG 17:525–532. doi:10.1038/ejhg.2008.203 CrossRefPubMed

Burwell RG, Dangerfield PH, Moulton A, Grivas TB (2011) Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy. Scoliosis 6:26. doi:10.1186/1748-7161-6-26 CrossRefPubMedPubMedCentral

10.

Talens RP, Boomsma DI, Tobi EW, Kremer D, Jukema JW, Willemsen G, Putter H, Slagboom PE, Heijmans BT (2010) Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J 24:3135–3144. doi:10.1096/fj.09-150490 CrossRefPubMed

11.

Posey KL, Alcorn JL, Hecht JT (2014) Pseudoachondroplasia/COMP—translating from the bench to the bedside. Matrix Biol J Int Soc Matrix Biol 37C:167–173. doi:10.1016/j.matbio.2014.05.006 CrossRef

12.

Briggs MD, Hoffman SM, King LM, Olsen AS, Mohrenweiser H, Leroy JG, Mortier GR, Rimoin DL, Lachman RS, Gaines ES et al (1995) Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene. Nat Genet 10:330–336. doi:10.1038/ng0795-330 CrossRefPubMed

13.

Hecht JT, Nelson LD, Crowder E, Wang Y, Elder FF, Harrison WR, Francomano CA, Prange CK, Lennon GG, Deere M et al (1995) Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia. Nat Genet 10:325–329. doi:10.1038/ng0795-325 CrossRefPubMed

14.

Hecht JT, Makitie O, Hayes E, Haynes R, Susic M, Montufar-Solis D, Duke PJ, Cole WG (2004) Chondrocyte cell death and intracellular distribution of COMP and type IX collagen in the pseudoachondroplasia growth plate. J Orthop Res 22:759–767. doi:10.1016/j.orthres.2003.11.010 CrossRefPubMed

15.

Fendri K, Patten SA, Kaufman GN, Zaouter C, Parent S, Grimard G, Edery P, Moldovan F (2013) Microarray expression profiling identifies genes with altered expression in adolescent idiopathic scoliosis. Eur Spine J 22:1300–1311. doi:10.1007/s00586-013-2728-2 CrossRefPubMedPubMedCentral

16.

Fendri K, Moldovan F (2011) Potential role of COMP as a biomarker for adolescent idiopathic scoliosis. Med Hypotheses 76:762–763. doi:10.1016/j.mehy.2011.01.038 CrossRefPubMed

17.

Gerdhem P, Topalis C, Grauers A, Stubendorff J, Ohlin A, Karlsson KM (2015) Serum level of cartilage oligomeric matrix protein is lower in children with idiopathic scoliosis than in non-scoliotic controls. Eur Spine J 24:256–261. doi:10.1007/s00586-014-3691-2 CrossRefPubMed

18.

Wong CC, Caspi A, Williams B, Craig IW, Houts R, Ambler A, Moffitt TE, Mill J (2010) A longitudinal study of epigenetic variation in twins. Epigenetics 5:516–526CrossRefPubMedPubMedCentral

19.

Cheng J, Wang Y, Zhou K, Wang L, Li J, Zhuang Q, Xu X, Xu L, Zhang K, Dai D, Zheng R, Li G, Zhang A, Gao S, Duan S (2014) Male-specific association between dopamine receptor D4 gene methylation and schizophrenia. PLoS One 9:e89128. doi:10.1371/journal.pone.0089128 CrossRefPubMedPubMedCentral

20.

Bornstein P (1992) Thrombospondins: structure and regulation of expression. FASEB J 6:3290–3299CrossRefPubMed

21.

DiCesare P, Hauser N, Lehman D, Pasumarti S, Paulsson M (1994) Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon. FEBS Lett 354:237–240CrossRefPubMed

22.

Kipnes J, Carlberg AL, Loredo GA, Lawler J, Tuan RS, Hall DJ (2003) Effect of cartilage oligomeric matrix protein on mesenchymal chondrogenesis in vitro. Osteoarthr Cartil 11:442–454CrossRefPubMed

23.

Chen FH, Thomas AO, Hecht JT, Goldring MB, Lawler J (2005) Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins. J Biol Chem 280:32655–32661. doi:10.1074/jbc.M504778200 CrossRefPubMedPubMedCentral

24.

Otteby KE, Holmquist E, Saxne T, Heinegard D, Hesselstrand R, Blom AM (2013) Cartilage oligomeric matrix protein-induced complement activation in systemic sclerosis. Arthritis Res Ther 15:R215. doi:10.1186/ar4410 CrossRefPubMedPubMedCentral

25.

Briggs MD, Chapman KL (2002) Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations. Hum Mutat 19:465–478. doi:10.1002/humu.10066 CrossRefPubMed

Title: Quantitative evaluation of the relationship between COMP promoter methylation and the susceptibility and curve progression of adolescent idiopathic scoliosis
Authors: Sai-hu Mao
Bang-ping Qian
Benlong Shi
Ze-zhang Zhu
Yong Qiu
Publication date: 01-02-2018
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 2/2018
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-017-5309-y

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Quantitative evaluation of the relationship between COMP promoter methylation and the susceptibility and curve progression of adolescent idiopathic scoliosis

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2018

Invariance of head-pelvis alignment and compensatory mechanisms for asymptomatic adults older than 49 years

Coronal plane trunk asymmetry is associated with whole-body sagittal alignment in healthy young adolescents before pubertal peak growth

Answer to the Letter to the Editor of T. Kawada concerning “Risk factors for sciatica leading to hospitalization” by U. Euro et al. Eur Spine J (2017). doi:10.1007/s00586-017-5182-8

Rapidly increasing incidence in scoliosis surgery over 14 years in a nationwide sample

Letter to the Editor concerning “Scoliosis convexity and organ anatomy are related” by T. P. C. Schlösser et al. (Eur Spine J; 2017: doi:10.1007/s00586-017-4970-5)

Incidence and risk factors for postoperative shoulder imbalance in scoliosis: a systematic review and meta-analysis