中国修复重建外科杂志

中国修复重建外科杂志

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

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目的 探讨 IL-6 基因启动子区-174 位点多态性与青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)易感性、支具矫形疗效的相关性,分析其可能的机制。 方法 以 2013 年 1 月–2016 年 1 月收治并符合选择标准的 182 例 AIS 患者,以及同期体检的无脊柱异常青少年 210 例,作为研究对象。检测所有研究对象 IL-6 基因启动子区-174 位点基因型,血清 IL-6 水平,股骨颈及腰椎骨密度(bone mineral density,BMD),骨代谢参数骨碱性磷酸酶(bone alkaline phosphatase,BALP)、骨钙素(bone gla protein,BGP)、抗酒石酸酸性磷酸酶 5b(tartrate resistant acid phosphatase 5b,TRACP-5b),尿钙(Ca)、尿肌酐(Cr)水平并计算尿 Ca/Cr。根据是否患 AIS 以及基因型检测结果将研究对象分别分为 AIS 组和对照组以及 GG 型、CG 型、CC 型组,根据支具治疗有无进展,将 AIS 患者分为进展组和无进展组;对以上检测指标分别进行统计学分析。 结果 AIS 组及对照组仅 AIS 家族史、股骨颈及腰椎 BMD 比较,差异有统计学意义(P<0.05)。根据治疗 1 年后检查结果,182 例 AIS 患者分为无进展组(110 例)和进展组(72 例);单因素分析显示,两组 IL-6 基因启动子区-174 等位基因、IL-6 基因启动子区-174 基因型、股骨颈及腰椎 BMD、IL-6、TRACP-5b、尿 Ca、尿 Ca/Cr 比较,差异有统计学意义(P<0.05);进一步多因素分析显示,腰椎 BMD、TRACP-5b、尿 Ca 是支具矫形疗效的影响因素(P<0.05)。根据基因检测结果,所有研究对象分为 GG 型 264 例、CG 型 104 例、CC 型 24 例。其中,GG 型携带者 IL-6、TRACP-5b、尿 Ca、尿 Ca/Cr 显著高于 CG 型和 CC 型(P<0.05),股骨颈及腰椎 BMD 显著降低(P<0.05)。CG 型携带者仅腰椎 BMD 显著低于 CC 型(P<0.05)。 结论 IL-6 基因启动子区-174 位点多态性与 AIS 易感性不相关,但与支具治疗后的脊柱侧凸进展相关但不独立相关,携带 G 基因者出现脊柱侧凸进展风险更高,其机制可能是 IL-6 基因启动子区-174 位点基因型影响 IL-6 的表达水平,并通过骨代谢中的骨吸收影响 BMD。

Objective To analyze the correlation between the polymorphism on interleukin 6 (IL-6) gene promoter region-174 locus and adolescent idiopathic scoliosis (AIS), including the susceptibility, the bracing effectiveness, and the possible mechanism. Methods The 182 AIS patients and 210 healthy controls who met the inclusion criteria between January 2013 and January 2016 were collected as research objects. The genotype of IL-6 gene promoter region-174 locus, the serum IL-6, the bone mineral density (BMD) of femoral neck and vertebrae (L1–4), and the bone metabolism parameters, including bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate resistant acid phosphatase 5b (TRACP-5b), urine Ca, and urine Ca/Cr, were detected. All research objects were divided into the AIS group and the control group according to whether they had AIS, the GG, CG, CC groups according to their genotype, and progression-free group and progression group according to the therapeutic effectiveness of 1-year bracing treatment. Statistical analysis for the indexes were conducted respectively. Results There were significant differences in AIS history, BMD of femoral neck and lumbar vertebrae between the AIS group and control group (P<0.05). According to the therapeutic effecitveness of 1-year bracing treatment, 182 AIS patients were divided into progression-free group in 110 cases and progression group in 72 cases. The results of single factor analysis showed that there were significant differences in the genotype and allele distribution of IL-6 gene promoter region-174 locus, BMD of femoral neck and lumbar vertebrae, IL-6, TRACP-5b, urine Ca, and urine Ca/Cr between the progression-free group and progression group (P<0.05). The results of multivariable analysis showed that the BMD of lumbar vertebrae, TRACP-5b, and urine Ca were the influencing factors of bracing efficacy (P<0.05). According to the results of genotype detection, all research objects were divided into GG group in 264 cases, CG group in 104 cases, and CC group in 24 cases. The IL-6, TRACP-5b, urine Ca, and urine Ca/Cr of GG type carriers were higher and BMD of femoral neck and lumbar vertebrae were lower when compared with the CG and CC type carriers (P<0.05). The BMD of lumbar vertebrae of CG type carriers was lower than that of CC type carriers (P<0.05). Conclusion The polymorphism of IL-6 genepromoter region-174 locus wasn’t correlated with the AIS susceptibility, but it was correlated (not independently correlated) with the scoliosis progression under bracing treatment, and the risk for G-carried patients was higher. The mechanism may be that the polymorphism affected the IL-6 expression level and eventually affected the BMD of AIS patients through the bone metabolism.

关键词: 青少年特发性脊柱侧凸; IL-6 基因多态性; 支具矫形; 疗效; 骨密度

Key words: Adolescent idiopathic scoliosis; interleukin 6 polymorphism; bracing; effectiveness; bone mineral density

引用本文: 高军胜, 张陆, 刘志昂, 姚帅辉, 高松明. 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. 中国修复重建外科杂志, 2018, 32(6): 678-684. doi: 10.7507/1002-1892.201710054 复制

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1. Horne JP, Flannery R, Usman S. Adolescent idiopathic scoliosis: diagnosis and management. Am Fam Physician, 2014, 89(3): 193-198.
2. Weiss HR, Karavidas N, Moramarco M, et al. Long-term effects of untreated adolescent idiopathic scoliosis: A review of the literature. Asian Spine J, 2016,10(6):1163-1169.
3. Negrini S, Minozzi S, Bettany-Saltikov J, et al. Braces for idiopathic scoliosis in adolescents. Cochrane Database Syst Rev, 2015, (6): CD006850.
4. Zhang Y, Yang Y, Dang X, et al. Factors relating to curve progression in female patients with adolescent idiopathic scoliosis treated with a brace. Eur Spine J, 2015, 24(2): 244-248.
5. Mahaudens P, Raison M, Banse X, et al. Effect of long-term orthotic treatment on gait biomechanics in adolescent idiopathic scoliosis. Spine J, 2014, 14(8): 1510-1519.
6. Marginean CO, Banescu C, Voidazan S, et al. IL-6 572 C/G, 190 C/T, and 174 G/C gene polymorphisms in children’s malnutrition. J Pediatr Gastroenterol Nutr, 2014, 59(5): 666-673.
7. Saxena M, Agrawal CG, Srivastava N, et al. Interleukin-6 (IL-6)-597 A/G (rs1800797) & -174 G/C (rs1800795) gene polymorphisms in type 2 diabetes. Indian J Med Res, 2014, 140(1): 60-68.
8. Lorentzon M, Lorentzon R, Nordström P. Interleukin-6 gene polymorphism is related to bone mineral density during and after puberty in healthy white males: a cross-sectional and longitudinal study. J Bone Miner Res, 2000, 15(10): 1944-1999.
9. 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. Spine (Phila Pa 1976), 2007, 32(24): 2700-2702.
10. Nikolova ST, Yablanski VT, Vlaev EN, et al. Association between IL-6 and MMP3 common genetic polymorphisms and idiopathic scoliosis in Bulgarian patients: a case-control Study. Spine (Phila Pa 1976), 2016, 41(9): 785-791.
11. Mórocz M, Czibula A, Grózer ZB, et al. Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis. Spine (Phila Pa 1976), 2011, 36(2): E123-130.
12. Liu Z, Tang NL, Cao XB, et al. Lack of association between the promoter polymorphisms of MMP-3 and IL-6 genes and adolescent idiopathic scoliosis: a case-control study in a Chinese Han population. Spine (Phila Pa 1976), 2010, 35(18): 1701-1705.
13. 刘臻. 青少年特发性脊柱侧弯与瘦素、白介素-6、基质金属蛋白酶3基因多态性及血清瘦素、可溶性瘦素受体相关性研究. 南京: 南京大学, 2010.
14. Zhao J, Yang M, Li M. Association of IL-6 and MMP-3 gene polymorphisms with susceptibility to adolescent idiopathic scoliosis: a meta-analysis. J Genet, 2016, 95(3): 573-579.
15. Pourabbas Tahvildari B, Erfani MA, Nouraei H, et al. Evaluation of bone mineral status in adolescent idiopathic scoliosis. Clin Orthop Surg, 2014, 6(2): 180-184.
16. Ishida K, Aota Y, Mitsugi N, et al. Relationship between bone density and bone metabolism in adolescent idiopathic scoliosis. Scoliosis, 2015, 10: 9.
17. Yip BH, Yu FW, Wang Z, et al. Prognostic value of bone mineral density on curve progression: a longitudinal cohort study of 513 girls with adolescent idiopathic scoliosis. Sci Rep, 2016, 6: 39220.
18. Li XF, Li H, Liu ZD, et al. Low bone mineral status in adolescent idiopathic scoliosis. Eur Spine J, 2008, 17(11): 1431-1440.
19. 吴健华, 王渭君, 付桂兵, 等. 伴综合征脊柱侧凸患者手术治疗的风险评估及疗效分析. 中国脊柱脊髓杂志, 2009, 19(6): 437-441.
20. Murakami M, Nishimoto N. IL-6 inhibitors prevent bone loss and cartilage degeneration in rheumatoid arthritis. Clin Calcium, 2015, 25(12): 1851-1857.
21. 杨锋, 孙玉华, 刘佃滨, 等. 骨质疏松患者骨碱性磷酸酶、钙、磷代谢变化及与牙槽骨骨密度的相关性. 中国骨质疏松杂志, 2017, 23(9): 1160-1166.
22. 陈小香, 谭新, 邓伟民. 骨质疏松症患者骨密度与血清25羟维生素D的相关性研究.中国骨质疏松杂志, 2017, 23(7): 851-855.
23. 周洁, 李茵茵, 车晓琪, 等. 老年男性骨代谢生化指标和骨密度的关系. 中华老年多器官疾病杂志, 2011, 10(2): 132-134.
24. Ni Y, Li H, Zhang Y, et al. Association of IL-6 G-174C polymorphism with bone mineral density. J Bone Miner Metab, 2014, 32(2): 167-173.
25. Wang Z, Yang Y, He M, et al. Association between interleukin-6 gene polymorphisms and bone mineral density: a meta-analysis. Genet Test Mol Biomarkers, 2013, 17(12): 898-909.