428 APOE4 and Prevalence of Degenerative Cervical Myelopathy: A Propensity Score-Matched Genetic Case-Control Study in the UK Biobank Cohort

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: 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. Propensity score-matching based on age and sex was used to capture an equal number of candidates with positive control outcomes for which possession of APOE e4 is known to increase the odds (dementia, hyperlipidaemia, and ischaemic heart disease), and one negative control with no known association with APOE (diaphragmatic hernia). We then conducted logistic regression of DCM or positive/control status against each APOE genotype (compared to reference genotype e3e3), adjusting for age, sex, array-type, assessment centre and measurement batch. RESULTS: Population characteristics of DCM cases (N=541). The most prevalent APOE genotype was e3e3 (58.9%), followed by e3e4 (23.8%), e2e3 (9.4%), e2e4 (3.7%), e4e4 (3.1%), and e2e2 (0.9%). 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:3.69,CI:3.08-4.40). APOE genotypes showed the expected associations with positive and negative control disease outcomes. CONCLUSIONS: We found a strong positive association between APOE genotype and DCM status. The APOE e4 variant and its biochemical correlates may be a novel biomarker to screen for high-risk individuals to include in randomised controlled trials for preventative interventions, and who would benefit most from APOE e4-targeting therapies.