Abstract
BackgroundThe 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.MethodsWe 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.ResultsOnly 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.ConclusionOur 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.
Highlights
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
Single-nucleotide polymorphisms (SNPs) are common genomic DNA variations in populations, and Single nucleotide polymorphism (SNP) located within functional regions of a gene may result in amino acid substitution and gene expression, which may be associated with susceptibility to diseases [15]
Stratified analyses between rs143384 and chronic postsurgical pain (CPSP) risk We evaluated the correlation between the GDF5 gene SNP rs143384 and CPSP risk in different subgroups (Table 3)
Summary
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. Shin et al reported that rs143383 was not associated with primary knee osteoarthritis in a Korean population [21], and Tsuzou et al reported a similar finding in Greek Caucasians of no significant differences in the subgroup stratified by sex [22] Another two SNPs, rs224332 and rs224333, located in the GDF5 gene were identified as related to hip dysplasia in Chinese women [23]. A recent genome-wide study by Meng et al suggests that rs143384 in the GDF5 gene is associated with knee pain in the UK Biobank, allele A is a risk factor [27], and SNP rs143384 in the 5′UTR region can affect GDF5 expression [28], indicating that the GDF5 gene is a potential risk factor for orthopedic CPSP
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