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GDF5 基因常见变异与慢性术后疼痛易感性的关系。

The effect of common variants in GDF5 gene on the susceptibility to chronic postsurgical pain.

机构信息

Department of Pain, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Xi'an, Shaanxi, China.

出版信息

J Orthop Surg Res. 2021 Jul 1;16(1):420. doi: 10.1186/s13018-021-02549-5.

Abstract

BACKGROUND

The growth differentiation factor 5 (GDF5) gene regulates the growth of neuronal axons and dendrites and plays a role in the inflammatory response and tissue damage. The gene may also be associated with chronic postsurgical pain. This study aimed to reveal the relationship between SNPs in the GDF5 gene and orthopedic chronic postsurgical pain in Han Chinese population based on a case-control study.

METHODS

We genotyped 8 SNPs within GDF5 gene in 1048 surgical patients with chronic postsurgical pain as the case group and 2062 surgical patients who were pain free as the control group. SNP and haplotypic analyses were performed, and stratified analyses were conducted to determine the correlations between significant SNPs and clinical characteristics.

RESULTS

Only rs143384 in the 5'UTR of GDF5 was identified as significantly associated with increased susceptibility to chronic postsurgical pain, and the risk of A allele carriers was increased approximately 1.35-fold compared with that of G allele carriers. Haplotypes AGG and GGG in the LD block rs143384-rs224335-rs739329 also showed similar association patterns. Furthermore, we found that rs143384 was significantly correlated with chronic postsurgical pain in the subgroup aged ≤ 61 years, subgroup with a BMI ≤ 26, subgroup with no-smoking or no pain history, and subgroup with a drinking history.

CONCLUSION

Our study provided supportive evidence that genetic variations in the GDF5 gene are potential genetic factors that can increase the risk of chronic postsurgical pain in the Han Chinese population, but further research is necessary to elucidate the underlying mechanism.

摘要

背景

生长分化因子 5(GDF5)基因调节神经元轴突和树突的生长,在炎症反应和组织损伤中发挥作用。该基因也可能与慢性术后疼痛有关。本研究旨在通过病例对照研究,揭示汉族人群 GDF5 基因中的 SNPs 与骨科慢性术后疼痛之间的关系。

方法

我们对 1048 例慢性术后疼痛患者(病例组)和 2062 例无疼痛患者(对照组)的 GDF5 基因内 8 个 SNPs 进行了基因分型。进行了 SNP 和单倍型分析,并进行了分层分析,以确定显著 SNPs 与临床特征之间的相关性。

结果

仅 GDF5 5'UTR 中的 rs143384 被确定为与慢性术后疼痛易感性增加显著相关,A 等位基因携带者的风险约增加 1.35 倍,而 G 等位基因携带者的风险增加 1.35 倍。LD 块 rs143384-rs224335-rs739329 中的单倍型 AGG 和 GGG 也显示出类似的关联模式。此外,我们发现 rs143384 与年龄≤61 岁、BMI≤26、无吸烟或无疼痛史以及有饮酒史的亚组慢性术后疼痛显著相关。

结论

本研究提供了支持性证据,表明 GDF5 基因中的遗传变异是汉族人群慢性术后疼痛的潜在遗传因素,但需要进一步研究阐明其潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69a4/8247225/f4181fdd14e1/13018_2021_2549_Fig1_HTML.jpg

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