Genotype-dependent miR-499/SOX5 axis regulation and its association with chronic low back pain risk and severity
Journal of Orthopaedic Surgery and Research · 7 Aug 2026
† Impact is the editorial-priority score. All scores are out of 100. Clinical is a stored clinical-importance score from the earlier method; it has not been recalculated.
Why it matters
This is basic-science/genetic biomarker research relevant to understanding CLBP susceptibility, not a treatment study, so it has limited immediate bearing on surgical decision-making but may inform future biomarker or precision-medicine research.
The evidence
This case-control study genotyped 180 chronic low back pain (CLBP) patients and 180 healthy controls for the miR-499 rs3746444 polymorphism and measured miR-499 and SOX5 expression in blood. The C allele and mutant genotypes (TC/CC) were associated with increased CLBP risk (CC genotype OR=3.457, P=0.002), and miR-499 was upregulated while SOX5 was downregulated specifically in CLBP patients carrying the C allele, with miR-499 levels correlating with pain (VAS) and disability (ODI) scores. Lab experiments (RIP, luciferase assay) confirmed SOX5 as a direct target of miR-499, but the authors are explicit that this is correlational genetic/molecular association work, not proof that this pathway causes pain.
CLBP risk associated with rs3746444 genotype: Odds ratio 3.457 (95% CI 1.592 to 7.506; units not reported). Interpret in the study's stated comparison; this alone does not establish a treatment's causal effect.
Why this rigour score?
Case-control
Methods at a glance
Recorded assessment- Confounding adjustmentMultivariable regression
- Covariate balance confirmedNot reported
- Outcome assessors blindedMet
- Comparable start of follow-upNot applicable
- Adequate statistical powerMet
- Prospective registrationNot reported
Not reported does not mean not done. Checks have different weights; this is not a count of boxes ticked.
How to read this assessment
The recorded methods are shown alongside the published score. A verified point-by-point calculation is not available for this version of the appraisal.
Checklist from the stored appraisal. “Not met” describes the recorded criterion; it does not always produce a deduction. This overview supports reading the full study.
For journal club
1.If a patient's CC genotype at rs3746444 were known, would that change how aggressively you pursue psychosocial or mechanical risk factor modification, given the authors' own caution that genetics is just one piece of a biopsychosocial picture?
2.Given that miR-499 levels correlated with VAS and ODI but were measured in peripheral blood rather than disc tissue, would you trust this as a future disease-activity biomarker before local tissue studies validate it?
Original publication title
Genotype-dependent miR-499/SOX5 axis regulation and its association with chronic low back pain risk and severity