Association between GDF5 single nucleotide polymorphism rs143383 and chronic lower back pain




Phillips, Nicole R.
Aryal, Subhash
Licciardone, John C.


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Introduction. Low back pain presents a unique and ongoing challenge for patients and physicians. Of those who experience an episode of low back pain, 10% go on to develop persistent chronic low back pain (CLBP). However, the cause of this progression is not understood and it is unclear why the clinical manifestation of CLBP differs across individuals. There is a large body of evidence demonstrating the role of genetics as a risk factor CLBP. Growth factor differentiation factor 5 (GDF5) is a protein involved in the growth and development of bone and cartilage. A variant of GDF5, single-nucleotide polymorphism (SNP) rs143383 has been implicated with increased susceptibility and severity of musculoskeletal disorders such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Considering that the cause of low back pain often involves musculoskeletal pathology, rs143383 may be implicated with symptomatology and the progression to persistent CLBP. Objective. This study seeks to determine whether the rs143383 SNP is associated with pain severity in CLBP. We hypothesize that subjects with the CC genotype experience higher levels of pain compared to the TT and CT genotypes. Methods. This project is an observational cohort study based on data retrieved from The Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION). Subjects were divided into three groups, TT, CT, and CC. Average pain levels based on the Numerical Rating Scale (NRS) for low back pain were compared among the groups. Results. Using a general linear model, we found that the rs143383 SNP was significantly associated with NRS scores (P = 0.001). We also found that the CC genotype had a statistical higher mean NRS score than the CT (P = 0.0370) and TT (P = 0.0004) genotypes. However, when the data was adjusted for race, ethnicity, gender and age, no significance was found between rs143383 and NRS scores. Conclusion. Our findings indicate that there is no association between the GDF5 rs143383 polymorphism after adjusting for race and ethnicity. We were unable to complete a stratified analysis due to the distribution of participants in each strata. Larger studies should consider a stratified analysis to determine whether there is an association between rs143383 and CLBP within different ethnicities and racial groups.