Abstract
Purpose
To explore whether the suppressor of cytokine signaling-3 (SOCS3) gene polymorphisms are associated with the susceptibility and abnormal growth pattern of adolescent idiopathic scoliosis (AIS).
Methods
Three hundred and ninety eight AIS girls aged 10–18 years old were enrolled, and 367 age-matched healthy girls were recruited as controls. Only patients who had Cobb angles larger than 20º were included in this study. Anthropometric parameters including body weight, height, and body mass index (BMI) were measured for AIS girls. Rs4969198 was selected as tagSNP to cover all of the related polymorphisms on SOCS3. Genotyping was performed using PCR-based Invader assay with the probe sets designed and synthesized by third wave. The genotyping results were read with an ABI PRISM7900HT sequence detection system (Applied Biosystems, Foster City, CA). A subgroup of 322 skeletally mature AIS patients who did not received bracing or any other conservative treatment previously were analyzed to define the contribution of rs4969168 on curve severity, body height, body weight, and BMI.
Results
Rs4969198 was successfully genotyped. No significant difference of genotype frequencies from the Hardy–Weinberg equilibrium (HWE) test was noted for the AIS patients or the normal controls. Neither the genotype nor the allele frequencies of rs49691968 were significantly different between the AIS patients and the normal controls. Rs4969168 was not found to be associated with age, curve severity of scoliosis, and body height. AIS patients with AA genotype had significantly higher body weight and BMI than the patients with AG and GG genotype (P = 0.014).
Conclusions
The SOCS3 gene polymorphisms are not associated with the occurrence of AIS, but the gene polymorphism (rs4969168) is associated with abnormal growth pattern of AIS, indicating that SOCS3 gene might be a disease-modifying gene of AIS.
Similar content being viewed by others
References
Cheung CSK, Lee WTK, Tse YK et al (2003) Abnormal peri-pubertal anthropometric measurements and growth pattern in adolescent idiopathic scoliosis: a study of 598 patients. Spine 28:2152–2157
Mao SH, Jiang J, Sun X et al (2011) Timing of menarche in Chinese girls with and without adolescent idiopathic scoliosis: current results and review of the literature. Eur Spine J 20:260–265
Carlsson B, Ankarberg C, Rosberg S et al (1997) Serum leptin concentrations in relation to pubertal development. Arch Dis Child 77:396–400
Di Carlo C, Tommaselli GA, De Filippo E et al (2002) Menstrual status and serum leptin levels in anorectic and in menstruating women with low body mass indexes. Fertil Steril 78:376–382
Qiu Y, Sun X, Qiu XS et al (2007) Decreased circulating leptin level and its association with body and bone mass in girls with adolescent idiopathic scoliosis. Spine 24:2703–2710
Mórocz M, Czibula A, Grózer ZB et al (2011) Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis. Spine 36(2):E123–E130 (Phila Pa 1976)
Liang G, Gao W, Liang A et al (2012) Normal leptin expression, lower adipogenic ability, decreased leptin receptor and hyposensitivity to leptin in adolescent idiopathic scoliosis. PLoS One 7(5):e36648
Liu Z, Tam Liu Z, Sun GQ et al (2012) Abnormal leptin bioavailability in adolescent idiopathic scoliosis: an important new finding. Spine 37(7):599–604 (Phila Pa 1976)
Mori H, Hanada R, Hanada T et al (2004) Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 10:739–743
Lorentzon M, Greenhalgh CJ, Mohan S et al (2005) Reduced bone mineral density in SOCS-2-deficient mice. Pediatr Res 57:223–226
Ocaka L, Zhao C, Reed JA et al (2008) Assignment of two loci for autosomal dominant adolescent idiopathic scoliosis to chromosomes 9q31.2-q34.2 and 17q25.3-qtel. J Med Genet 45:87–92
Salehi LB, Mangino M, De Serio S et al (2002) Assignment of a locus for autosomal dominant idiopathic scoliosis (IS) to human chromosome 17p11. Hum Genet 111:401–404
Miller NH, Justice CM, Marosy B et al (2005) Identification of candidate regions for familial idiopathic scoliosis. Spine 30:1181–1187
Alden KJ, Marosy B, Nzegwu N et al (2006) Idiopathic scoliosis: identification of candidate regions on chromosome 19p13. Spine 31:1815–1819
Takahashi Y, Kou I, Takahashi A et al (2011) A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet 43(12):1237–1240
Fan YH, Song YQ, Chan D et al (2012) SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese. J Hum Genet 57(4):244–246
Jiang H, Qiu X, Dai J et al (2013) Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis susceptibility in a Han Chinese population. Eur Spine J 22(2):282–286
Bjørbaek C, Elmquist JK, Frantz JD et al (1998) Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell 1:619–625
Bjørbaek C, Elmquist JK, Frantz JD et al (1999) The role of SOCS-3 in leptin signaling and leptin resistance. J Biol Chem 274:30059–30065
Talbert ME, Langefeld CD, Ziegler J et al (2009) Polymorphisms near SOCS3 are associated with obesity and glucose homeostasis traits in Hispanic Americans from the insulin resistance atherosclerosis family study. Hum Genet 125:153–162
Tang W, Zou JJ, Chen XF et al (2011) Association of two polymorphisms within and near SOCS3 gene with obesity in three nationalities in Xinjiang province of China. Acta Pharmacol Sin 32(11):1381–1386
Cheng JC, Tang NL, Yeung HY et al (2007) Genetic association of complex traits: using idiopathic scoliosis as an example. Clin Orthop Relat Res 462:38–44
Acknowledgment
This work was supported by the Natural Science Foundation of China (81170002). The Manuscript submitted does not contain information about medical device(s)/drug(s). No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
F. Zhu and J. Qiao contributed equally to this work.
Rights and permissions
About this article
Cite this article
Zhu, F., Qiao, J., Qiu, X. et al. Lack of association between suppressor of cytokine signaling-3 gene polymorphism and susceptibility and curve severity of adolescent idiopathic scoliosis. Eur Spine J 23, 2432–2436 (2014). https://doi.org/10.1007/s00586-014-3452-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00586-014-3452-2