APOE4 and prevalence of degenerative cervical myelopathy: A genetic case-control study in the UK Biobank cohort.

INTRODUCTION

APOE ε4 expression mediates a pro-inflammatory response that has been associated with poorer outcomes in patients with degenerative cervical myelopathy (DCM). However, no study has yet assessed the association between APOE genotype and prevalence of DCM on a population level which may be useful for screening and treatment purposes.

METHODS

ICD-10 codes were used to ascertain DCM cases and positive control outcomes for which APOE ε4 is known to increase the odds (dementia, hypercholesterolemia and ischemic heart disease) and one negative control with no known association with APOE (diaphragmatic hernia). Multivariate logistic regression was performed of DCM or positive/negative control status against each APOE genotype (vs ε3ε3), adjusting for age, sex, array-type, assessment centre and measurement batch. Sensitivity analyses assessed the association between ε4 allele dosage (homozygous vs. heterozygous/ε4-negative) and DCM severity, indicated by cervical spine surgery history, short-term postoperative outcomes, number of hospital admissions, and critical care utilization within 6 months of DCM diagnosis.

RESULTS

Overall, 929 DCM cases were identified. The most prevalent APOE genotype was ε3ε3 (57.6%), followed by ε3ε4 (24.3%), ε2ε3 (12.2%), ε2ε4 (2.5%) and ε4ε4 (2.4%). In logistic regression, the ε4ε4 genotype was associated with increased odds of having DCM (OR 1.48, 95% CI 1.03-2.11). APOE genotypes showed the expected associations with positive and negative control disease outcomes. Sensitivity analyses revealed associations between ε4 and indicators of increased DCM severity, but these results did not reach statistical significance after accounting for multiple testing.

CONCLUSIONS

We found a strong positive association between APOE genotype and DCM status. The APOE ε4 variant may serve as a novel biomarker for screening high-risk individuals and as a personalized therapeutic target in DCM.