Introduction: APOE e4 expression mediates a pro-inflammatory response that contributes to 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: A genetic case-control study design was used to achieve our objective. DCM cases were ascertained through ICD-10 codes and univariate analyses were performed to describe their baseline demographic and clinical characteristics based on APOE genotype. ICD-10 codes were also used to identify positive control outcomes for which possession of APOE ε4 is known to increase the odds (dementia, hypercholesterolemia and ischemia, and one negative control with no known association with APOE (diaphragmatic hernia). We then conducted logistic regression of DCM or positive/negative control status against each APOE genotype (compared to the reference genotype 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, low physical activity, or low grip strength recorded within 6 months of DCM diagnosis.
Results: Nine hundred and twenty-nine DCM cases were identified. The most prevalent APOE genotype was ε3ε3 (57.56%), followed by ε3ε4 (24.3%), ε2ε3 (12.18%), ε2ε4 (2.53%) and ε4ε4 (2.38%). Apart from smoking, we observed no differences in genotypic frequencies based on demographic/clinical characteristics. In logistic regression, genotypes ε3ε4 and ε4ε4 were associated with increased odds of having DCM (OR: 1.48, CI:1.03-2.11). APOE genotypes showed the expected associations with positive and negative control disease outcomes. Sensitivity analyses showed that DCM patients with the ε4ε4 genotype were more likely to have low grip strength and cervical spine surgery than ε4 heterozygotes and ε4-negative patients.
Conclusion : We found a strong positive association between APOE genotype and DCM status. The APOE ε4 variant and its biochemical correlates may be used as a novel biomarker to screen for high-risk individuals and a novel personalized therapeutic target in DCM.
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