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

Association between MMP-3 rs3025058/IL-6 rs1800795 single nucleotide polymorphisms and idiopathic scoliosis: a Meta-analysis

目的 :探讨基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)rs3025058和白介素-6(interleukin-6,IL-6)rs1800795单核苷酸多态性(single nucleotide polymorphism,SNP)与特发性脊柱侧凸(idiopathic scoliosis,IS)易感性的相关性。方法 :计算机检索Pubmed、Cochrane Library、Web of Science、Databases@Ovid(OVID)、中国期刊数据库(CNKI)和万方数据库,检索时间为建库到2017年7月31日。搜集关于MMP-3 rs3025058和IL-6 rs1800795 SNP与IS易感性关系的病例-对照研究文献,纳入文献的方法学质量采用纽卡斯尔渥太华量表进行评价。提取各研究中MMP-3 rs3025058和IL-6 rs1800795位点的等位基因频数及不同基因型频数,用Revman 5.3软件进行统计分析,计算出不同遗传模型的比值比(OR)和95%可信区间(95%CI)。并按照人种将纳入人群分为亚洲人种和高加索人种两个亚组进行分析。结果:共纳入7篇文献,6篇为英文文献,1篇为中文文献,方法学质量评价7篇文献均在5颗星以上。7篇文献共包括1349例IS患者(IS组)和1609例对照(对照组)。Meta分析结果显示,MMP-3 rs3025058 SNP的等位基因5A和基因型5A5A与IS易感性有关[5A vs. 6A,OR=1.18,95%CI:1.03~1.35,P=0.01;5A5A vs. 6A6A,OR=1.68,95%CI:1.23~2.30,P=0.001;5A5A vs. 5A6A+6A6A,OR=1.64,95%CI:1.08~2.47,P=0.02]。亚组分析结果显示在亚洲人群中,5A5A vs. 6A6A,OR=1.85,95%CI:1.13~3.02,P=0.01;5A5A vs. 5A6A+6A6A,OR=1.81,95%CI:1.11~2.97,P=0.02。在高加索人群中,5A vs. 6A,OR=1.22,95%CI:1.00~1.49,P=0.05;5A5A vs. 6A6A,OR=1.57,95%CI:1.05~2.36,P=0.003。IL-6rs1800795 SNP与IS易感性没有关联[C vs. G,OR=0.71,95%CI:0.38~1.30,P=0.27]。结论:MMP-3 rs3025058位点的等位基因5A和基因型5A5A与IS的易感性存在相关性,尤其是在高加索人群中;IL-6 rs1800795位点的基因多态性与IS的发病无明显相关。

Objectives： To explore whether IL-6 rs1800795 and MMP-3 rs3025058 single nucleotide polymorphisms（SNP） are associated with the susceptibility to idiopathic scoliosis（IS）. Methods： Databases including Pubmed, Cochrane Library, Web of Science, Databases@Ovid（OVID）, China National Knowledge Infrastructure（CNKI） and Wanfang databases were used to collect case-control studies which evaluated the association between IL-6 rs1800795 and MMP-3 rs3025058 SNP from inception to July 31, 2017. The quality of the included literatures was evaluated by Newcastle-Ottawa Scale. After the data of the allelic frequency and genotypic frequency among the SNPs were abstracted, both overall and stratified（by population） Meta-analyses were performed by Revman 5.3 software. Summary odd ratios（OR） and corresponding 95% confidence intervals（95%CI） were estimated in allelic and genotypic comparisons. Besides, subgroup analysis between Caucasian and Asian populations was conducted according to ethnicity. Results： Six English literatures and one Chinese literature were included, methodological quality assessment of all which were more than or equal to 5 stars. Seven studies meeting the inclusion criteria contained 1349 cases and 1609 controls for Meta-analysis. The results showed allele 5A and genotype 5A5A of MMP-3 rs3025058 were significantly associated with IS： 5A vs. 6A, OR=1.18, 95%CI： 1.03-1.35, P=0.01; 5A5A vs. 6A6A, OR=1.68, 95%CI： 1.23-2.30, P=0.001; 5A5A vs. 5A6A＋6A6A, OR=1.64, 95%CI： 1.08-2.47, P=0.02. When stratified into Caucasian and Asian populations, there was significant association in both populations, but the results in Caucasian population were closer to overall： in Asian population, 5A5A vs. 6A6A, OR=1.85, 95%CI： 1.13-3.02, P=0.01; 5A5A vs. 5A6A＋6A6A, OR=1.81, 95%CI： 1.11-2.97, P=0.02; in Caucasian population, 5A vs. 6A, OR=1.22, 95%CI： 1.00-1.49, P=0.05; 5A5A vs. 6A6A, OR=1.57, 95%CI： 1.05-2.36, P=0.003. But no significant association was detected between IL-6 rs1800795 and IS（C vs. G, OR=0.71, 95%CI： 0.38-1.30, P=0.27）. Conclusions： Our results suggest that the allelic of 5A and genotype 5A5A in MMP-3 rs3025058 are significantly associated with IS susceptibility especially in Caucasian population. Besides, the currently available studies can not supply enough evidence to prove an overall significant association of IL-6 rs1800795 polymorphism with risk of IS.