Gao Junsheng, Zhang Lu, Liu Zhiang, Yao Shuaihui, Gao Songming
Department of Orthopedics, Zhengzhou People's Hospital, Zhengzhou Henan, 450000,
Department of Orthopedics, Zhengzhou People's Hospital, Zhengzhou Henan, 450000, P.R.China.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2018 Jun 15;32(6):678-684. doi: 10.7507/1002-1892.201710054.
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.
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 ), 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.
There were significant differences in AIS history, BMD of femoral neck and lumbar vertebrae between the AIS group and control group ( <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 ( <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 ( 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 ( <0.05). The BMD of lumbar vertebrae of CG type carriers was lower than that of CC type carriers ( <0.05).
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.
分析白细胞介素6(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(AIS)之间的相关性,包括易感性、支具治疗效果及可能机制。
收集2013年1月至2016年1月期间符合纳入标准的182例AIS患者和210例健康对照作为研究对象。检测IL-6基因启动子区-174位点的基因型、血清IL-6、股骨颈和腰椎(L )的骨密度(BMD)以及骨代谢参数,包括骨碱性磷酸酶(BALP)、骨钙素(BGP)、抗酒石酸酸性磷酸酶5b(TRACP-5b)、尿钙和尿钙/肌酐。所有研究对象根据是否患有AIS分为AIS组和对照组,根据基因型分为GG、CG、CC组,根据1年支具治疗的疗效分为无进展组和进展组。分别对各项指标进行统计分析。
AIS组与对照组在AIS病史、股骨颈和腰椎BMD方面存在显著差异(<0.05)。根据1年支具治疗的疗效,182例AIS患者分为无进展组110例和进展组72例。单因素分析结果显示,无进展组与进展组在IL-6基因启动子区-174位点的基因型和等位基因分布、股骨颈和腰椎BMD、IL-6、TRACP-5b、尿钙和尿钙/肌酐方面存在显著差异(<0.05)。多变量分析结果显示,腰椎BMD、TRACP-5b和尿钙是支具疗效的影响因素(<0.05)。根据基因型检测结果,所有研究对象分为GG组264例、CG组104例、CC组24例。与CG型和CC型携带者相比,GG型携带者血清IL-6、TRACP-5b、尿钙和尿钙/肌酐水平较高,股骨颈和腰椎BMD较低(<0.05)。CG型携带者的腰椎BMD低于CC型携带者(<0.05)。
IL-6基因启动子区-174位点多态性与AIS易感性无关,但与支具治疗下脊柱侧凸进展相关(非独立相关),携带G等位基因患者的风险更高。其机制可能是该多态性影响IL-6表达水平,最终通过骨代谢影响AIS患者的骨密度。