A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand
A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand
复制标题
GDF5 基因变异与膝关节、髋关节和手部骨关节炎之间关联的综合荟萃分析
DOI：
10.1007/s00011-015-0818-9
复制
发表时间：
2015-06-01
影响因子：
6.7
通讯作者：
Ma, Jie
中科院分区：
文献类型：
--
作者：
Zhang, Rui;Yao, Jianfeng;Ma, Jie
目的：许多研究报告了GDF 5与骨关节炎（OA）的关联，但产生了一些分歧的结果，他们的解释可能不是直截了当的。方法：我们调查了GDF 5和OA之间的关联使用荟萃分析技术，结合所有已发表的数据，到2014年11月。来自11个研究团队的16个独立样本提供了SNP rs 143383（位于GDF 5的5 '-UTR）与膝关节、髋关节和手OA的数据。该标志物的病例和对照总数分别为膝关节OA 7，965例和12，747例，髋关节OA 6，363例和9，727例，手部OA 4，335例和5，991例。结果：采用随机效应模型，膝关节OA患者与对照组rs 143383 T等位基因存在显著性差异（小计OR = 1.18，95%CI =1.10-1.27，P=1.84 × 10（-6））。对于手部OA，在合并人群中也观察到SNP rs 143383的中度相关性（小计OR = 1.09，95% CI = 1.02-1.16，P = 0.01）。然而，在两项联合研究中发现髋关节OA的汇总OR无统计学显著性（小计OR = 1.22，95% CI = 0.97-1.53，P = 0.09）和欧洲研究（总计OR = 1.16，95%CI = 0.91-1.48，P = 0.23）。结论：我们的研究结果表明，GDF 5的SNP rs 143383是膝关节和手部OA的一个令人信服的危险因素，并为GDF 5在OA病因学中提供了进一步的支持。需要进一步努力在体外和体内鉴定GDF 5的功能变体。
Objective:A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward.Methods:We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5'-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity.Results:Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10-1.27, P=1.84 × 10(-6)). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02-1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97-1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91-1.48, P = 0.23).Conclusions:Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.