Lack of association between the CHL1 gene and adolescent idiopathic scoliosis susceptibility in Han Chinese: a case-control study

BMC Musculoskeletal Disorders

Yong Qiu¹  Yang Yu¹  Bin Wang¹  Bang-ping Qian¹  Ze-zhang Zhu¹  Feng Lv¹  Xu-sheng Qiu¹ 

[1] Spine Surgery, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

关键词: Polymorphism;    Chinese;    CHL1;    Adolescent idiopathic scoliosis;   

Others  :  1128841
DOI  :  10.1186/1471-2474-15-38

 received in 2013-02-22, accepted in 2014-02-06,  发布年份 2014

【 摘 要 】

Background

A previous genome-wide association study (GWAS) suggested a strong association between the single nucleotide polymorphism (SNP) rs10510181 in the proximity of the gene encoding a cell adhesion molecule with homology to L1CAM (CHL1) and adolescent idiopathic scoliosis (AIS) in Caucasians. To clarify the role of CHL1 in the etiopathogenesis of AIS, we performed a case-control replication study in a Han Chinese population.

Methods

Five hundred female AIS patients between 10 and 18 years of age, as well as 500 age- and sex-matched controls were included. This study was conducted as a 2-stage case-control analysis: initial screening for the association between AIS and SNPs in and around the CHL1 gene (186 cases and 169 controls) followed by a confirmation test (314 cases and 331 controls). rs10510181 and 4 SNPs (rs2055314, rs331894, rs2272522, and rs2272524) in the CHL1 gene were selected for genotyping.

Results

Putative associations were shown between AIS and rs10510181, rs2055314, and rs2272522 in stage I. However, the associations were not confirmed in stage II. For rs10510181, the genotype frequencies were GG 28.8%, GA 46.2%, and AA 25.0% in AIS patients and GG 29.8%, GA 48.8%, and AA 21.4% in controls. No significant difference was found in genotype distribution between cases and controls (P = 0.39). Similarly, the genotype and allele distribution were comparable between case and control for rs2055314 and rs2272522.

Conclusions

There was no statistical association between polymorphisms of the CHL1 gene and idiopathic scoliosis in a Chinese population.

【 授权许可】

   
2014 Qiu et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Asher MA, Burton DC: Adolescent idiopathic scoliosis: natural history and long term treatment effects. Scoliosis 2006, 1(1):2. BioMed Central Full Text
• [2]Lowe TG, Edgar M, Margulies JY, Miller NH, Raso VJ, Reinker KA, Rivard CH: Etiology of idiopathic scoliosis: current trends in research. J Bone Joint Surg Am 2000, 82-A(8):1157-1168.
• [3]Wang WJ, Yeung HY, Chu WC, Tang NL, Lee KM, Qiu Y, Burwell RG, Cheng JC: Top theories for the etiopathogenesis of adolescent idiopathic scoliosis. J Pediatr Orthop 2011, 31(1 Suppl):S14-27.
• [4]Kesling KL, Reinker KA: Scoliosis in twins. A meta-analysis of the literature and report of six cases. Spine (Phila Pa 1976) 1997, 22(17):2009-2014. discussion 2015
• [5]Riseborough EJ, Wynne-Davies R: A genetic survey of idiopathic scoliosis in Boston, Massachusetts. J Bone Joint Surg Am 1973, 55(5):974-982.
• [6]Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, et al.: A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet 2011, 43(12):1237-1240.
• [7]Miller NH, Justice CM, Marosy B, Doheny KF, Pugh E, Zhang J, Dietz HC, Wilson AF: Identification of candidate regions for familial idiopathic scoliosis. Spine (Phila Pa 1976) 2005, 30(10):1181-1187.
• [8]Ocaka L, Zhao C, Reed JA, Ebenezer ND, Brice G, Morley T, Mehta M, O'Dowd J, Weber JL, Hardcastle AJ, et al.: Assignment of two loci for autosomal dominant adolescent idiopathic scoliosis to chromosomes 9q31.2-q34.2 and 17q25.3-qtel. J Med Genet 2008, 45(2):87-92.
• [9]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(10):1131-1136.
• [10]Qiu XS, Tang NL, Yeung HY, Lee KM, Hung VW, Ng BK, Ma SL, Kwok RH, Qin L, Qiu Y, et al.: Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 2007, 32(16):1748-1753.
• [11]Chen Z, Tang NL, Cao X, Qiao D, Yi L, Cheng JC, Qiu Y: Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population. Eur J Hum Genet 2009, 17(4):525-532.
• [12]Takahashi Y, Matsumoto M, Karasugi T, Watanabe K, Chiba K, Kawakami N, Tsuji T, Uno K, Suzuki T, Ito M, et al.: Replication study of the association between adolescent idiopathic scoliosis and two estrogen receptor genes. J Orthop Res 2011, 29(6):834-837.
• [13]Takahashi Y, Matsumoto M, Karasugi T, Watanabe K, Chiba K, Kawakami N, Tsuji T, Uno K, Suzuki T, Ito M, 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(7):1055-1058.
• [14]Jiang H, Qiu X, Dai J, Yan H, Zhu Z, Qian B, Qiu Y: Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis susceptibility in a Han Chinese population. Eur Spine J 2013, 22(2):282-286.
• [15]Sharma S, Gao X, Londono D, Devroy SE, Mauldin KN, Frankel JT, Brandon JM, Zhang D, Li QZ, Dobbs MB, et al.: Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet 2011, 20(7):1456-1466.
• [16]Chen S, Mantei N, Dong L, Schachner M: Prevention of neuronal cell death by neural adhesion molecules L1 and CHL1. J Neurobiol 1999, 38(3):428-439.
• [17]Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rub U, Shattuck D, Salamon G, Kudo LC, Ou J, et al.: Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science 2004, 304(5676):1509-1513.
• [18]Chen QY, Chen Q, Feng GY, Lindpaintner K, Chen Y, Sun X, Chen Z, Gao Z, Tang J, He L: Case-control association study of the close homologue of L1 (CHL1) gene and schizophrenia in the Chinese population. Schizophr Res 2005, 73(2–3):269-274.
• [19]Siu King Cheung C, Tak Keung Lee W, Kit Tse Y, Ping Tang S, Man Lee K, Guo X, Qin L, Chun Yiu Cheng J: Abnormal peri-pubertal anthropometric measurements and growth pattern in adolescent idiopathic scoliosis: a study of 598 patients. Spine (Phila Pa 1976) 2003, 28(18):2152-2157.
• [20]Kingsmore SF, Lindquist IE, Mudge J, Beavis WD: Genome-wide association studies: progress in identifying genetic biomarkers in common, complex diseases. Biomark Insights 2007, 2:283-292.
• [21]McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, Hirschhorn JN: Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008, 9(5):356-369.
• [22]Siontis KC, Patsopoulos NA, Ioannidis JP: Replication of past candidate loci for common diseases and phenotypes in 100 genome-wide association studies. Eur J Hum Genet 2010, 18(7):832-837.
• [23]Wright AG, Demyanenko GP, Powell A, Schachner M, Enriquez-Barreto L, Tran TS, Polleux F, Maness PF: Close homolog of L1 and neuropilin 1 mediate guidance of thalamocortical axons at the ventral telencephalon. J Neurosci 2007, 27(50):13667-13679.
• [24]Huang X, Zhu LL, Zhao T, Wu LY, Wu KW, Schachner M, Xiao ZC, Fan M: CHL1 negatively regulates the proliferation and neuronal differentiation of neural progenitor cells through activation of the ERK1/2 MAPK pathway. Mol Cell Neurosci 2011, 46(1):296-307.
• [25]Heyden A, Angenstein F, Sallaz M, Seidenbecher C, Montag D: Abnormal axonal guidance and brain anatomy in mouse mutants for the cell recognition molecules close homolog of L1 and NgCAM-related cell adhesion molecule. Neuroscience 2008, 155(1):221-233.
• [26]Potoupnis M, Kapetanos G, Kimiskidis VK, Symeonides PP: Is the central nervous system a causative factor in idiopathic scoliosis? Stud Health Technol Inform 2002, 91:10-11.
• [27]Herman R, Mixon J, Fisher A, Maulucci R, Stuyck J: Idiopathic scoliosis and the central nervous system: a motor control problem. The Harrington lecture. Scoliosis Research Society. Spine (Phila Pa 1976) 1985 1983, 10(1):1-14.
• [28]Veldhuizen AG, Wever DJ, Webb PJ: The aetiology of idiopathic scoliosis: biomechanical and neuromuscular factors. Eur Spine J 2000, 9(3):178-184.