Adolescent idiopathic scoliosis (AIS) is a structural curvature of the spine that was estimated to affect millions of children worldwide. Recent study shows that the functional variant rs10738445 could add to the risk of AIS through the regulation of BNC2 gene. This study aims to investigate whether the rs10738445 of BNC2 gene is a functional susceptible locus for AIS in the Chinese population and to further clarify the association of the BNC2 expression with the curve severity. SNP rs10738445 was genotyped in 1952 patients and 2492 controls, and further replicated in 693 patients and 254 controls. We found that patients have a significantly higher frequency of CC than the controls (21.9 vs. 17.7%, p = 0.004 for stage 1; 12.6 vs. 7.9%, p = 0.03 for stage 2). Allele C can significantly add to the risk of AIS with an OR of 1.14–1.24. AIS patients were found to have significantly higher BNC2 expression than the controls. The BNC2 expression was significantly correlated with the curve severity (r = 0.316, p = 0.02). In conclusion, our study suggests a functional role of BNC2 in the development and progression of the spinal deformity in AIS.
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Ahn UM, Ahn NU, Nallamshetty L, Buchowski JM, Rose PS, Miller NH, Kostuik JP, Sponseller PD (2002) The etiology of adolescent idiopathic scoliosis. Am J Orth 31:387–395
Buchan JG, Alvarado DM, Haller GE, Cruchaga C, Harms MB, Zhang T, Willing MC, Grange DK, Braverman AC, Miller NH, Morcuende JA, Tang NL, Lam TP, Ng BK, Cheng JC, Dobbs MB, Gurnett CA (2014) Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis. Hum Mol Genet 23:5271–5282
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 17:525–532
Gurnett CA, Alaee F, Bowcock A, Kruse L, Lenke LG, Bridwell KH, Kuklo T, Luhmann SJ, Dobbs MB (2009) Genetic linkage localizes an adolescent idiopathic scoliosis and pectus excavatum gene to chromosome 18 q. Spine 34:E94–E100
Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J, Qiu X, Sharma S, Takimoto A, Ogura Y, Jiang H, Yan H, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Hosono N, Tsuji T, Suzuki T, Sudo H, Kotani T, Yonezawa I, Londono D, Gordon D, Herring JA, Watanabe K, Chiba K, Kamatani N, Jiang Q, Hiraki Y, Kubo M, Toyama Y, Tsunoda T, Wise CA, Qiu Y, Shukunami C, Matsumoto M, Ikegawa S (2013) Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet 45:676–679
Miller NH, Mims B, Child A, Milewicz DM, Sponseller P, Blanton SH (1996) Genetic analysis of structural elastic fiber and collagen genes in familial adolescent idiopathic scoliosis. J Orth Res 14:994–999
Morcuende JA, Minhas R, Dolan L, Stevens J, Beck J, Wang K, Weinstein SL, Sheffield V (2003) Allelic variants of human melatonin 1 A receptor in patients with familial adolescent idiopathic scoliosis. Spine 28:2025–2028
Ogura Y, Kou I, Miura S, Takahashi A, Xu L, Takeda K, Takahashi Y, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yonezawa I, Yanagida H, Taneichi H, Zhu Z, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Hosogane N, Okada E, Iida A, Nakajima M, Sudo A, Chiba K, Hiraki Y, Toyama Y, Qiu Y, Shukunami C, Kamatani Y, Kubo M, Matsumoto M, Ikegawa S (2015) A functional SNP in BNC2 is associated with adolescent idiopathic scoliosis. Am J Hum Genet 97:337–342
Parent S, Newton PO, Wenger DR (2005) Adolescent idiopathic scoliosis: etiology, anatomy, natural history, and bracing. Inst Cour Lect 54:529–536
Qiu XS, Tang NL, Yeung HY, Qiu Y, Qin L, Lee KM, Cheng JC (2006) The role of melatonin receptor 1B gene (MTNR1B) in adolescent idiopathic scoliosis–a genetic association study. Stud Health Tech Informat 123:3–8
Raggio CL, Giampietro PF, Dobrin S, Zhao C, Dorshorst D, Ghebranious N, Weber JL, Blank RD (2009) A novel locus for adolescent idiopathic scoliosis on chromosome 12p. J Orth Res 27:1366–1372
Sharma S, Gao X, Londono D, Devroy SE, Mauldin KN, Frankel JT, Brandon JM, Zhang D, Li QZ, Dobbs MB, Gurnett CA, Grant SF, Hakonarson H, Dormans JP, Herring JA, Gordon D, Wise CA (2011) Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet 20:1456–1466
Sharma S, Londono D, Eckalbar WL, Gao X, Zhang D, Mauldin K, Kou I, Takahashi A, Matsumoto M, Kamiya N, Murphy KK, Cornelia R, Group TSC, Japan Scoliosis Clinical Research G, Herring JA, Burns D, Ahituv N, Ikegawa S, Gordon D, Wise CA (2015) A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females. Nat Commun 6:6452.
Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Chiba K, Hosono N, Kamatani N, Tsunoda T, Toyama Y, Kubo M, Matsumoto M, Ikegawa S (2011) A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet 43:1237–1240
Vanhoutteghem A, Bouche C, Maciejewski-Duval A, Hervé F, Djian P (2011) Basonuclins and disco: Orthologous zinc finger proteins essential for development in vertebrates and arthropods. Biochimie 93:127–133
Wang H, Wu Z, Zhuang Q, Fei Q, Zhang J, Liu Y, Wang Y, Ding Y, Qiu G (2008) Association study of tryptophan hydroxylase 1 and arylalkylamine N-acetyltransferase polymorphisms with adolescent idiopathic scoliosis in Han Chinese. Spine 33:2199–2203
Weinstein SL (1989) Adolescent idiopathic scoliosis: prevalence and natural history. Inst Cour Lect 38:115–128
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
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
This work was supported by the Natural Science Foundation of China (No. 81501849, No. 81661168013, No. 81171672, & No. 81501932), Natural Science Foundation of Jiangsu Province (BK20150099), and Nanjing Medical Science and technology development Foundation (Grant No. YKK15060).
Conflict of interest
The authors have no conflict of interest to declare.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Communicated by S. Hohmann.
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Xu, L., Xia, C., Qin, X. et al. Genetic variant of BNC2 gene is functionally associated with adolescent idiopathic scoliosis in Chinese population. Mol Genet Genomics 292, 789–794 (2017). https://doi.org/10.1007/s00438-017-1315-3
- Adolescent idiopathic scoliosis
- Functional variant