Research Progress of Single Nucleotide Polymorphism and Adolescent Idiopathic Scoliosis
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摘要: 青少年特发性脊柱侧凸（ adolescent idiopathic scoliosis，AIS）在全世界范围内的发病率为1%～3%，患病群体基数大，且给患者造成生理和心理的双重痛苦。大量研究表明，遗传因素可能在AIS的发生发展中起重要作用。单核苷酸多态性（single nucleotide polymorphisms，SNPs）与AIS相关性的研究成为近年来医学分子遗传学研究的重点。对AIS易感基因的SNPs进行深入研究，有助于探索AIS预防、诊断和治疗的新策略。就目前基因SNPs与AIS的相关性研究进展作一综述。
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关键词:
- 青少年特发性脊柱侧凸 /
- 基因 /
- 多态性 /
- 单核苷酸 /
- 民族
Abstract: The incidence of adolescent idiopathic scoliosis （AIS） worldwide is 1%～3%, the base of the diseased population is large, and it causes both physical and psychological pains to patients. Numerous studies have shown that genetic factors may play an important role in the occurrence and development of AIS. The correlation between single nucleotide polymorphisms （SNPs） and AIS is the focus of medical molecular research in recent years. In-depth research on the SNPs of susceptibility genes will help to explore new strategies for the prevention, diagnosis and treatment of AIS. This article reviews the research advances concerning gene SNPs and AIS susceptibility.-
Key words:
- Adolescent idiopathic scoliosis /
- Genes /
- Polymorphism /
- Single nucleotide /
- Nationality
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表 1 ESR家族基因多态性与AIS易感性的关系
Table 1. The relationship between ESR family gene polymorphism and susceptibility to AIS
作者 年份 国家 人种（病例组/正常组） 基因/SNP rs号（等位基因） 阳性/阴性关联 Janusz等[6] 2013 波兰 白种人（287/182） ESR1/rs9340799（A/G）
ESR1/rs2234693（T/C）阴性关联 Takahashi等[7] 2011 日本 黄种人（798/637） ESR1/rs9340799（A/G）
ESR2/rs1256120（C/T）阴性关联 Sobhan等[8] 2020 中国
日本
波兰
黄种人
（1640/1171）
（842/534）
（1000/811）
白种人
（287/182）
（287/182）
（248/243）ESR1/rs9340799（A/G）
ESR1/rs2234693（T/C）
ESR2/rs1256120（C/T）ESR1/rs9340799（A/G）可能
与黄种人有阳性关联，
其余阴性关联Zhao等[5] 2016 中国
日本
波兰黄种人（1016/777）
白种人（248/243）ESR2/rs1256120（C/T） 阴性关联 
下载: 导出CSV
表 2 骨代谢基因多态性与AIS易感性的关系
Table 2. The relationship between bone metabolism-related gene polymorphisms and susceptibility to AIS
作者 年份 国家 人种（病例组/正常组） 基因/SNP rs号（等位基因） 阳性/阴性关联 高军胜等[9] 2018 中国 黄种人（182/210） IL-6/rs1800795（G/C） 阴性关联 Sobhan等[16] 2019 伊朗 亚洲人（80/80） IL-6/rs1800795（G/C） 阴性关联 Sobhan等[16] 2019 韩国
匈牙利
保加利亚
意大利
中国
伊朗白种人（364/773）
亚洲人（1331/1324）
IL-6/rs1800795（G/C） 在白种人群中阳性关联 Sui等[13] 2016 中国 黄种人（200/200） IL-6/rs1800795（G/C）
MMP-3/rs3025058（5A/7A）IL-6/rs1800795与AIS是阴性关联；
MMP-3/rs3025058与AIS是阳性关联周传坤等[17] 2018 中国
保加利亚
匈牙利
韩国
意大利亚洲人
（678/602）
（687/694）
高加索人（284/613）
（284/613）IL-6/rs1800795（G/C）
MMP-3/rs3025058（5A/7A）IL-6/rs1800795与AIS是阴性关联；
MMP-3/rs3025058与AIS是阳性
关联，尤其是在高加索人群
下载: 导出CSV
表 3 多民族易感基因多态性与AIS易感性的关系
Table 3. The relationship between multi-ethnic susceptibility gene polymorphisms and susceptibility to AIS
作者 年份 国家 人种和样本量 基因/SNP rs号（等位基因） 阳性/阴性关联 Liu等[24] 2016 中国 黄种人（180/182） LBX1/rs11190870（C/T）
LBX1/rs1322331（T/G）
LBX1/rs4917933（A/G）
LBX1/rs625039（A/G）
LBX1/rs11190872（T/C）rs11190870、rs1322331与AIS
为阳性关联，其余为阴性关联Man等[23] 2018 中国 黄种人（319/201） LBX1/rs11190870（C/T）
SOX9/KCNJ2 rs12946942（G/T）
PAX3/EPHA4 rs13398147（C/T）
AJAP1/rs241215（T/A）
BNC2/rs3904778（C/G）
GPR126/rs6570507（A/G）
LBX1-AS1/rs678741 （A/G）LBX1/rs11190870
BNC2/rs3904778
GPR126/rs6570507；
LBX1-AS1/rs678741
与AIS为阳性关联，
其余为阴性关联Londono等[29] 2014 中国
美国
日本黄种人
（3771/15605）
非黄种人
（1388/2235）LBX1/rs11190870（C/T）
阳性关联 Chettier等[27] 2015 美国 白种人（620/1287） LBX1中的500个位点 rs11190870与AIS为阳性关联，
其余为阴性关联Grauers等[25] 2015 瑞典
丹麦白种人
（1739/1812）GPR126/rs6570507（A/G）
LBX1/rs11190870（C/T）
CHL1/rs10510181（A/G）
基因间/rs12946942（T/G）rs11190870与AIS为阳性关联，
其余为阴性关联Nada等[26] 2017 加拿大 白种人
（667/901）LBX1/rs11190870（C/T）
LBX1/rs7893223（T/C）
LBX1/rs594791（A/G）
LBX1/rs11190878（A/G）阳性关联 Jiang等[30] 2019 日本
中国
美国
瑞典
加拿大亚洲人
（7712/21529）
高加索人
（3699/5080）LBX1/rs11190870（C/T）
LBX1/rs11598564（A/G）
LBX1/rs678741（A/G）
LBX1/rs625039（A/G）rs11190870、
rs625039、
rs11598564
与AIS为阳性关联；
rs678741在AIS发生
中期保护作用。Li等[22] 2018 中国
日本
美国
瑞典
丹麦亚洲人
（3458/15279）
高加索人
（620/1287）
非以上两人种
（2412/2892）LBX1/rs11190870（C/T）
阳性关联 Kou等[28] 2018 日本
中国
美国
斯堪的纳维亚黄种人
（3991/29845）
高加索人
（2882/9071）GPR126/rs6570507（A/G）
阳性关联
下载: 导出CSV
表 4 女性特异性基因多态性与AIS易感性的关系
Table 4. The relationship between female-specific gene polymorphisms and susceptibility to AIS
下载: 导出CSV
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[1] Menger R P, Sin A H. Adolescent and idiopathic scoliosis [M]. Treasure Island （FL）: StatPearls, 2021: 29763083. [2] Essex R,Bruce G,Dibley M,et al. A systematic scoping review and textual narrative synthesis of long-term health-related quality of life outcomes for adolescent idiopathic scoliosis[J]. International Journal of Orthopaedic and Trauma Nursing,2021,40(3):100844. [3] Zamborsk R,Liščák B,Trepáč M,et al. Adolescent idiopathic scoliosis - future molecular-based diagnostic and prognostic testing[J]. Ortop Traumatol Rehabil,2019,21(4):253-260. doi: 10.5604/01.3001.0013.5070 [4] Mukhtar M,Sargazi S,Barani M,et al. Application of nanotechnology for sensitive detection of low-abundance single-nucleotide variations in genomic DNA:A review[J]. Nanomaterials (Basel),2021,11(6):1384. doi: 10.3390/nano11061384 [5] Zhao L,Roffey D M,Chen S. Association between the estrogen receptor beta (ESR2) rs1256120 single nucleotide polymorphism and adolescent idiopathic scoliosis:A systematic review and meta-analysis[J]. Spine,2017,42(11):871-878. doi: 10.1097/BRS.0000000000001932 [6] Janusz P,Kotwicki T,Andrusiewicz M,et al. XbaI and PvuII polymorphisms of estrogen receptor 1 gene in females with idiopathic scoliosis:No association with occurrence or clinical form[J]. PLoS One,2013,8(10):e76806. doi: 10.1371/journal.pone.0076806 [7] Takahashi Y,Matsumoto M,Karasugi T,et al. Replication study of the association between adolescent idiopathic scoliosis and two estrogen receptor genes[J]. J Orthop Res,2011,29(6):834-837. doi: 10.1002/jor.21322 [8] Sobhan M R,Mahdinezhad-Yazdi M,Dastgheib S A,et al. Association of ESRα XbaI A > G,ESRα PvuII T > C and ESRβ AlwNI T > C Polymorphisms with the risk of developing adolescent idiopathic scoliosis:A systematic review and genetic meta-analysis[J]. Revista Brasileira de Ortopedia,2020,55(1):8-16. doi: 10.1016/j.rboe.2018.03.001 [9] 高军胜,张陆,刘志昂,等. IL-6基因多态性与青少年特发性脊柱侧凸易感性及支具矫形疗效的相关性研究[J]. 中国修复重建外科杂志,2018,32(6):678-684. doi: 10.7507/1002-1892.201710054 [10] Murakami M,Nishimoto N. IL-6 inhibitors prevent bone loss and cartilage degeneration in rheumatoid arthritis[J]. Clin Calcium,2015,25(12):1851-1857. [11] Teles Filho R V,Abe G D M,Daher M T. Genetic Influence in disc degeneration - systematic review of literature[J]. Revista Brasileira de Ortopedia,2020,55(2):131-138. doi: 10.1055/s-0039-1692626 [12] Dai Z,Wang Y,Wu Z,et al. Female-specific susceptibility locus in BOC and SEC16B are associated with adolescent idiopathic scoliosis[J]. Spine (Phila Pa,1976),2021,46(22):e1178-e1184. [13] Sui W,Yang J,Huang Z,et al. Polymorphisms in promoter regions of MMP-3 and IL-6 genes are not associated to adolescent idiopathic scoliosis (AIS) gender bias[J]. Journal of Back and Musculoskeletal Rehabilitation,2017,30(3):559-563. doi: 10.3233/BMR-150309 [14] Mórocz M,Czibula A,Grózer Z B,et al. Association study of BMP4,IL6,Leptin,MMP3,and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis[J]. Spine (Phila Pa,1976),2011,36(2):E123-E130. [15] Aulisa L,Papaleo P,Pola E,et al. Association between IL-6 and MMP-3 gene polymorphisms and adolescent idiopathic scoliosis:A case-control study[J]. Spine (Phila Pa,1976),2007,32(24):2700-2702. [16] Sobhan M R,Mahdinezhad-Yazdi M,Dastgheib S A,et al. Association of the IL-6 -174G > C (rs1800795) polymorphism with adolescent idiopathic scoliosis:Evidence from a case-control study and meta-analysis[J]. Revista Brasileira De Ortopedia,2020,55(1):17-26. doi: 10.1055/s-0039-1700813 [17] 周传坤,高书涛,王鹏,等. MMP-3 rs3025058和IL-6 rs1800795单核苷酸多态性与特发性脊柱侧凸相关性的Meta分析[J]. 中国脊柱脊髓杂志,2018,28(3):219-227. doi: 10.3969/j.issn.1004-406X.2018.03.05 [18] Luo M,Zhang Y,Huang S,et al. The susceptibility and potential functions of the LBX1 gene in adolescent idiopathic scoliosis[J]. Front Genet,2020,11(1):614984. [19] Kou I,Takahashi Y,Johnson T A,et al. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis[J]. Nat Genet,2013,45(6):676-679. doi: 10.1038/ng.2639 [20] Zhao J,Li M,Bradfield J P,et al. The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature[J]. BMC Med Genet,2010,11(6):96. [21] Lettre G,Jackson A U,Gieger C,et al. Identification of ten loci associated with height highlights new biological pathways in human growth[J]. Nat Genet,2008,40(5):584-591. doi: 10.1038/ng.125 [22] Li Y L, Gao S J, Xu H, et al. The association of rs11190870 near LBX1 with the susceptibility and severity of AIS, a meta-analysis [J]. Int J Surg, 2018, 54（Pt A）: 193-200. [23] Man G C,Tang N L,Chan T F,et al. Replication study for the association of GWAS-associated loci with adolescent idiopathic scoliosis susceptibility and curve progression in a chinese population[J]. Spine (Phila Pa,1976),2019,44(7):464-471. [24] Liu S,Wu N,Zuo Y,et al. Genetic polymorphism of LBX1 is associated with adolescent idiopathic scoliosis in northern chinese Han population[J]. Spine (Phila Pa,1976),2017,42(15):1125-1129. [25] Grauers A,Wang J,Einarsdottir E,et al. Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis[J]. Spine J,2015,15(10):2239-2246. doi: 10.1016/j.spinee.2015.05.013 [26] Nada D,Julien C,Samuels M E,et al. A replication study for association of LBX1 locus with adolescent idiopathic scoliosis in French-Canadian population[J]. Spine (Phila Pa,1976),2018,43(3):172-178. [27] Chettier R,Nelson L,Ogilvie J W,et al. Haplotypes at LBX1 have distinct inheritance patterns with opposite effects in adolescent idiopathic scoliosis[J]. PLoS One,2015,10(2):e0117708. doi: 10.1371/journal.pone.0117708 [28] Kou I,Watanabe K,Takahashi Y,et al. A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis[J]. Sci Rep,2018,8(1):11575. doi: 10.1038/s41598-018-29011-7 [29] Londono D,Kou I,Johnson T A,et al. A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups[J]. J Med Genet,2014,51(6):401-406. doi: 10.1136/jmedgenet-2013-102067 [30] Jiang H,Yang Q,Liu Y,et al. Association between ladybird homeobox 1 gene polymorphisms and adolescent idiopathic scoliosis:A moose-compliant meta-analysis[J]. Medicine (Baltimore),2019,98(27):e16314. [31] Kruse L M,Buchan J G,Gurnett C A,et al. Polygenic threshold model with sex dimorphism in adolescent idiopathic scoliosis:The carter effect[J]. J Bone Joint Surg Am,2012,94(16):1485-1491. doi: 10.2106/JBJS.K.01450 [32] Regitz-Zagrosek V,Kararigas G. Mechanistic pathways of sex differences in cardiovascular disease[J]. Physiol Rev,2017,97(1):1-37. doi: 10.1152/physrev.00021.2015 [33] Chowdhury N U,Guntur V P,Newcomb D C,et al. Sex and gender in asthma[J]. Eur Respir Rev,2021,30(162):210067. doi: 10.1183/16000617.0067-2021 [34] Nebel R A,Aggarwal N T,Barnes L L,et al. Understanding the impact of sex and gender in Alzheimer's disease:A call to action[J]. Alzheimers Dement,2018,14(9):1171-1183. doi: 10.1016/j.jalz.2018.04.008 [35] Sharma S,Londono D,Eckalbar W L,et al. A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females[J]. Nature Communications,2015,6(1):6452. doi: 10.1038/ncomms7452 [36] Sizar O, Khare S, Goyal A, et al. Vitamin D Deficiency [M]. Treasure Island （FL）: StatPearls, 2021: 30335299. [37] Schwenk R W,Vogel H,Schürmann A. Genetic and epigenetic control of metabolic health[J]. Mol Metab,2013,2(4):337-347. doi: 10.1016/j.molmet.2013.09.002 [38] Sivakamasundari V,Kraus P,Sun W,et al. A developmental transcriptomic analysis of PAX1 and PAX9 in embryonic intervertebral disc development[J]. Biol Open,2017,6(2):187-199. [39] Xu L,Sheng F,Xia C,et al. Genetic variant of PAX1 gene is functionally associated with adolescent idiopathic scoliosis in the Chinese population[J]. Spine,2018,43(7):492-496. doi: 10.1097/BRS.0000000000002475 [40] Liu G,Liu S,Li X,et al. Genetic polymorphisms of PAX1 are functionally associated with different PUMC types of adolescent idiopathic scoliosis in a northern Chinese Han population[J]. Gene,2019,688(3):215-220. [41] Kou I,Otomo N,Takeda K,et al. Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese[J]. Nature Communications,2019,10(1):3685-3685. doi: 10.1038/s41467-019-11596-w [42] Yin X,Cheng H,Lin Y,et al. A weighted polygenic risk score using 14 known susceptibility variants to estimate risk and age onset of psoriasis in Han Chinese[J]. PLoS One,2015,10(5):e0125369. doi: 10.1371/journal.pone.0125369 [43] Sabik O L,Farber C R. Using GWAS to identify novel therapeutic targets for osteoporosis[J]. Transl Res,2017,181(5):15-26. [44] Zhang F R,Liu H,Irwanto A,et al. HLA-B*13:01 and the dapsone hypersensitivity syndrome[J]. N Engl J Med,2013,369(17):1620-1628. doi: 10.1056/NEJMoa1213096 [45] Ma X,Yang W,Gao Y,et al. Genetic origins and sex-biased admixture of the huis[J]. Mol Biol Evol,2021,38(9):3804-3819. doi: 10.1093/molbev/msab158 [46] 杨昭庆,禇嘉祐. 中国人类遗传多样性研究进展[J]. 遗传,2012,34(11):1351-1364. [47] Li Y H,Luo J Y,Fang B B,et al. Association between CCN1 gene polymorphism and acute coronary syndrome in Chinese Han and Uygur populations[J]. Hereditas,2021,158(1):16. doi: 10.1186/s41065-021-00180-2 [48] Wang T,Sun L,Xu L,et al. Prevalence of dyslipidemia and gene polymorphisms of ABCB1 and SLCO1B1 in Han,Uygur,Kazak,Hui,Tatar,Kirgiz,and Sibe populations with coronary heart disease in Xinjiang,China[J]. Lipids Health Dis,2021,20(1):116. doi: 10.1186/s12944-021-01544-3 [49] Peng Y,Wang S R,Qiu G X,et al. Research progress on the etiology and pathogenesis of adolescent idiopathic scoliosis[J]. Chin Med J (Engl),2020,133(4):483-493. doi: 10.1097/CM9.0000000000000652 -
