Renuka Chintapalli, BA, MA, MB BChir: No financial relationships to disclose
Introduction: APOE e4 expression has been shown to mediate 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 4 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 e3e3), adjusting for age, sex, array-type, assessment centre and measurement batch. Sensitivity analyses were performed to ascertain the association between e4 allele ‘dosage’ (homozygous vs heterozygous/e4 negative genotype) and DCM severity, as indicated by history of cervical spine surgery, low physical activity or low grip strength in either hand recorded within 6 months of DCM diagnosis.
Results: Nine hundred and twenty-nine DCM cases were identified. The most prevalent APOE genotype was e3e3 (57.56%), followed by e3e4 (24.3%), e2e3 (12.18%), e2e4 (2.53%) and e4e4 (2.38%). Apart from smoking, we observed no differences in genotypic frequencies based on demographic/clinical characteristics. In logistic regression, genotypes e3e4 and e4e4 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 e4e4 genotype were more likely to have low grip strength and cervical spine surgery than e4 heterozygotes and e4-negative patients.
Conclusion : We found a strong positive association between APOE genotype and DCM status. The APOE e4 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.