Dataset Information

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.

ABSTRACT: The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13-3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19-0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD.

SUBMITTER: Okubadejo NU

PROVIDER: S-EPMC9653490 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.

Okubadejo Njideka U NU Okunoye Olaitan O Ojo Oluwadamilola O OO Arabambi Babawale B Akinyemi Rufus O RO Osaigbovo Godwin O GO Abubakar Sani A SA Iwuozo Emmanuel U EU Wahab Kolawole W KW Agabi Osigwe P OP Agulanna Uchechi U Imarhiagbe Frank A FA Abiodun Oladunni V OV Achoru Charles O CO Adebowale Akintunde A AA Adeniji Olaleye O Akpekpe John E JE Ali Mohammed W MW Ani-Osheku Ifeyinwa I Arigbodi Ohwotemu O Balarabe Salisu A SA Bello Abiodun H AH Ekenze Oluchi S OS Erameh Cyril O CO Farombi Temitope H TH Fawale Michael B MB Komolafe Morenikeji A MA Nwani Paul O PO Nwazor Ernest O EO Nyandaiti Yakub Y Obehighe Emmanuel E EE Obiabo Yahaya O YO Odeniyi Olanike A OA Odiase Francis E FE Ojini Francis I FI Onwuegbuzie Gerald A GA Osemwegie Nosakhare N Oshinaike Olajumoke O OO Otubogun Folajimi M FM Oyakhire Shyngle I SI Taiwo Funlola T FT Williams Uduak E UE Ozomma Simon S Zubair Yusuf Y Hernandez Dena D Bandres-Ciga Sara S Blauwendraat Cornelis C Singleton Andrew A Houlden Henry H Hardy John J Rizig Mie M

NPJ Parkinson's disease 20221112 1

The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic a ...[more]

PMID: 36371506

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Project description:Alzheimer's disease (AD) age of onset (ADAOO) varies greatly between individuals, with unique causal mutations suggesting the role of modifying genetic and environmental interactions. We analyzed ~50 000 common and rare functional genomic variants from 71 individuals of the 'Paisa' pedigree, the world's largest pedigree segregating a severe form of early-onset AD, who were affected carriers of the fully penetrant E280A mutation in the presenilin-1 (PSEN1) gene. Affected carriers with ages at the extremes of the ADAOO distribution (30s-70s age range), and linear mixed-effects models were used to build single-locus regression models outlining the ADAOO. We identified the rs7412 (APOE*E2 allele) as a whole exome-wide ADAOO modifier that delays ADAOO by ~12 years (β=11.74, 95% confidence interval (CI): 8.07-15.41, P=6.31 × 10(-8), PFDR=2.48 × 10(-3)). Subsequently, to evaluate comprehensively the APOE (apolipoprotein E) haplotype variants (E1/E2/E3/E4), the markers rs7412 and rs429358 were genotyped in 93 AD affected carriers of the E280A mutation. We found that the APOE*E2 allele, and not APOE*E4, modifies ADAOO in carriers of the E280A mutation (β=8.24, 95% CI: 4.45-12.01, P=3.84 × 10(-5)). Exploratory linear mixed-effects multilocus analysis suggested that other functional variants harbored in genes involved in cell proliferation, protein degradation, apoptotic and immune dysregulation processes (i.e., GPR20, TRIM22, FCRL5, AOAH, PINLYP, IFI16, RC3H1 and DFNA5) might interact with the APOE*E2 allele. Interestingly, suggestive evidence as an ADAOO modifier was found for one of these variants (GPR20) in a set of patients with sporadic AD from the Paisa genetic isolate. This is the first study demonstrating that the APOE*E2 allele modifies the natural history of AD typified by the age of onset in E280A mutation carriers. To the best of our knowledge, this is the largest analyzed sample of patients with a unique mutation sharing uniform environment. Formal replication of our results in other populations and in other forms of AD will be crucial for prediction, follow-up and presumably developing new therapeutic strategies for patients either at risk or affected by AD.

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Dataset Information

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.

Publications

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.

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