Table 1.
List of diseases where an association with APOE variants has been identified using different models and approaches.
| Disease | Model/Approach | Conclusion |
|---|---|---|
| Carotid Atherosclerosis; progression of (Ma W. et al., 2022) | Logistic regression analysis | ε4 allele is independent risk factor for CAS in Han populations; the association is partly mediated through blood lipids. |
| Cerebral microbleeds (CMB) (Romero et al., 2014) | Framingham Original and Offspring cohort; MRI | Association of hypertension, CMB, low cholesterol and ε4 |
| Combat-Related Posttraumatic Stress Disorder (Kim et al., 2013) | Clinician-Administered PTSD and Combat Exposure Scales with an assessment of the severity of alcohol use; logistic regression analysis. | APOEε2 allele operates as a susceptibility gene for combat-related PTSD, with the relationship between alcohol use and PTSD differing according to the APOEε2 carrier status |
| Coronary artery disease (Ashiq and Ashiq, 2021) | Meta analysis; ε2 vs. ε3 & ε4 vs. ε3. | ε4 allele appears as a significant genetic risk factor for coronary artery disease while the ε2 allele is beneficial to alleviate the CAD risk |
| Dementia with Lewy bodies (Bras et al., 2014) | GWAS | APOE genetic locus, driven by ε4 allele, is the strongest genetic risk factor for DLB |
| Exceptional longevity (Garatachea et al., 2014) | Each genotype and allele compared with all other genotypes and alleles | ε4 allele decreases the likelihood of reaching EL among individuals of different ethnic/geographic origins. ε2 favors EL, at least in the Italian and Japanese cohorts. |
| Frontotemporal lobar degeneration (Rubino et al., 2013) | Meta analysis; ε4 carriers vs. non-ε4 carriers; ε4 carriers vs. ε3 carriers | Evidence for an association between the ε4 allele and frontotemporal lobar degeneration. |
| Glomerular filtration rate (eGFR) (Coto et al., 2013) | Modified Diet in Renal Disease formula; multivariate logistic regression analysis | ε4 allele is a genetic risk factor for impaired renal function among healthy elderly Spanish individuals |
| Incident dementia risk in late life and early-life educational attainment (Ma H. et al., 2022) | Cox proportional hazards models | Higher educational attainment in early life may attenuate the risk for dementia, particularly among people with high genetic predisposition (one or two ε4 alleles). |
| Incident MCI and Physical Activity (Krell-Roesch et al., 2016) | Cox proportional hazards models; Prospective cohort study | Higher risk of incident MCI in ε4 carriers compared to ε4 non-carriers who reported physical activity |
| Late life depression (Yen et al., 2007) | Questionnaire; multinomial logistic regression analysis | ε4 allele may be correlated with severe depression in the elderly |
| Metabolic syndrome (Carty et al., 2014) | Meta analysis | APOC1/APOE/TOMM40 significantly associated with MetS components overall |
| Mood disorders # Cardiometabolic disease (Amare et al., 2017) | Meta-GWASs; | APOE4 in a group of 24 pleotropic genes participates in biological mechanisms of mood disorders and cardiometabolic diseases |
| Non pathological cognitive aging (Davies et al., 2014) | GWAS | Both APOE (rs429358 and TOMM40 (rs11556505; as loci that were associated with cognitive agin) |
| Parkinson’s disease (Mata et al., 2014) | Cognitive test; Verbal learning | ε4 is a predictor of cognitive function in PD |
| Primary progressive aphasia and speech apraxia (Josephs et al., 2014) | Confirmed PPA, APOE genotyping and PiB PET | ε4 increases the risk of β-amyloid deposition in PPA and progressive speech apraxia but does not influence regional β-amyloid distribution or severity |
| Rheumatoid Arthritis (Chen et al., 2020) | CVD risk association | Lower risk for CVD in patients with ε2ε3 genotype compared to ε3ε4 |
| Schizophrenia (Allen et al., 2008) | Meta analysis; ε4 vs. ε3 | APOE in a group of 16 genes shows significant effect |
| TBI and deposition of Aβ (Nicoll et al., 1995) | Histological examination, APOE genotyping | The frequency of ε4 in those individuals with Aβ deposition following head injury (0.52) is higher than in most studies of Alzheimer’s disease |
| Vascular dementia (Chuang et al., 2010) | Cox proportional hazards models | ε4 allele is associated with an increased risk of Vascular Dementia in a dose dependent fashion |
| Vascular disease (Koopal et al., 2015) | ε2 heterozygosity vs. all other Е genotypes | Distinct modifier effect of APOEε4 on the relation between adiposity and lipids |
The statements in the third column are concise conclusions related, as much as possible, mostly to APOE, in case the association includes other genes or conditions. The Table should be considered incomplete since (1) it does not include studies published in 2023, and (2) numerous studies that have confirmed already established associations between APOE and CVD.