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Title: [Correlation analysis between interleukin 6 polymorphism and adolescent idiopathic scoliosis susceptibility and bracing effectiveness].
Author: Gao J, Zhang L, Liu Z, Yao S, Gao S.
Journal: Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi; 2018 Jun 15; 32(6):678-684. PubMed ID: 29905044.
Abstract:
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 (L _1-4), 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. 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。.

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