MAPT allele and haplotype frequencies in Nigerian Africans: Population distribution and association with Parkinson's disease risk and age at onset.

INTRODUCTION: The association between MAPT and PD risk may be subject to ethnic variability even within populations of similar geographical origin. Data on MAPT haplotype frequencies, and its association with PD risk in black Africans are lacking. We aimed to determine the frequencies of MAPT haplotypes and their role as risk factors for PD and age at onset in Nigerians. METHODS: The haplotype and genotype frequencies of MAPT rs1052553 were analysed in 907 individuals with PD and 1022 age-matched healthy controls from the Nigeria Parkinson's Disease Research network cohort. Clinical data related to PD included age at study, age at onset (AAO), and disease duration. RESULTS: The frequency of the H1 haplotype was 98.7% in PD, and 99.1% in controls (p = 0.19). The H2 haplotype was present in - 1.3% of PD and 0.9% of controls (p = 0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and AAO (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p = 0.23). CONCLUSIONS: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans but document its occurrence in Nigerians. The MAPT H1 haplotype was not associated with an increased risk or age at onset of PD in this cohort.

MAPT allele and haplotype frequencies in Nigerian Africans: population distribution and association with Parkinson's disease risk and age at onset.

Background: The microtubule-associated protein tau ( MAPT ) gene is critical because of its putative role in the causal pathway of neurodegenerative diseases including Parkinson's disease (PD). However, there is a lack of clarity regarding the link between the main H1 haplotype and risk of PD. Inconsistencies in reported association may be driven by genetic variability in the populations studied to date. Data on MAPT haplotype frequencies in the general population and association studies exploring the role of MAPT haplotypes in conferring PD risk in black Africans are lacking. Objectives: To determine the frequencies of MAPT haplotypes and explore the role of the H1 haplotype as a risk factor for PD risk and age at onset in Nigerian Africans. Methods: The haplotype and genotype frequencies of MAPT rs1052553 were analysed using PCR-based KASP™ in 907 individuals with PD and 1,022 age-matched neurologically normal controls from the Nigeria Parkinson's Disease Research (NPDR) network cohort. Clinical data related to PD included age at study, age at onset, and disease duration. Results: The frequency of the main MAPT H1 haplotype in this cohort was 98.7% in individuals with PD, and 99.1% in healthy controls (p=0.19). The H2 haplotype was present in 41/1929 (2.1%) of the cohort (PD - 1.3%; Controls - 0.9%; p=0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and age at onset (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p=0.23). Conclusions: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans, but document its occurrence in the Nigerian population (2.1%). In this cohort of black Africans with PD, the MAPT H1 haplotype was not associated with an increased risk or age at onset of PD.

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

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.

Normative data for ulnar nerve conduction and the influence of gender and height on ulnar nerve conduction velocity in healthy Nigerians.

Background: Despite the usefulness of ulnar nerve conduction studies in identifying disorders of ulnar nerves, there is a lack of normative values for the ulnar nerve in Nigerian population. Objective: The objective of the study was to generate normative values for motor and sensory ulnar nerve conduction studies (NCSs) in Nigerian population and to determine the influence of gender and height on ulnar nerve conduction velocity (NCV). Materials and Methods: A total of 200 healthy volunteers were selected after clinical evaluation to exclude common causes of ulnar neuropathy. We carried out NCS of ulnar nerves on all the healthy volunteers according to a standardized protocol. The NCS parameters included in the final analysis were amplitude, latency, NCV, and f-wave latency. Ethical approval was obtained for the study. Results: The mean ulnar nerve sensory velocity was 55.22 ± 5.67 with 2.5 and 97.5 percentile of 46.9 and 70.1, respectively. The mean latency of the ulnar nerve (sensory) was 2.97 ± 0.62 with 2.5 and 97.5 percentile of 2.00 and 4.52, respectively. The mean amplitude of the ulnar nerve (sensory) was 35.56 ± 9.97 with 2.5 and 97.5 percentile of 15.9 and 57.7, respectively). The ulnar NCV was significantly (P = 0.0202) higher in male. Mild inverse correlation (r = 0.2) was found between ulnar NCV and height of the participants (P = 0.0089). Conclusion: In the Nigerian population, normative values of motor and sensory ulnar nerve conduction parameters are similar to the existing values in the literature. The ulnar NCV appeared to be influenced by height and gender.

Résumé Contexte: Malgré l'utilité des études de conduction du nerf ulnaire pour identifier les troubles des nerfs ulnaire, il y a un manque de normative valeurs pour le nerf ulnaire dans la population nigériane. Objectif: L'objectif de l'étude était de générer des valeurs normatives pour les moteurs et études de conduction sensorielle du nerf ulnaire (NCS) dans la population nigériane et pour déterminer l'influence du sexe et de la taille sur le nerf ulnaire vitesse de conduction (NCV). Matériel et méthodes: Un total de 200 volontaires sains ont été sélectionnés après évaluation clinique pour exclure causes courantes de neuropathie ulnaire. Nous avons réalisé une NCS des nerfs ulnaire sur tous les volontaires sains selon un protocole standardisé.Les paramètres NCS inclus dans l'analyse finale étaient l'amplitude, la latence, la NCV et la latence de l'onde f. L'approbation éthique a été obtenue pour le étude. Résultats: La vitesse sensorielle moyenne du nerf ulnaire était de 55,22 ± 5,67 avec 2,5 et 97,5 percentile de 46,9 et 70,1, respectivement. La moyenne la latence du nerf ulnaire (sensoriel) était de 2,97 ± 0,62 avec 2,5 et 97,5 percentile de 2,00 et 4,52, respectivement. L'amplitude moyenne de l'ulnaire nerf (sensoriel) était de 35,56 ± 9,97 avec 2,5 et 97,5 percentile de 15,9 et 57,7, respectivement). Le NCV ulnaire était significativement (P = 0,0202)plus élevé chez les hommes. Une légère corrélation inverse (r = 0,2) a été trouvée entre la NCV ulnaire et la taille des participants (P = 0,0089). Conclusion: dans la population nigériane, les valeurs normatives des paramètres de conduction du nerf ulnaire moteur et sensoriel sont similaires aux valeurs existantes dans le Littérature. Le NCV ulnaire semble être influencé par la taille et le sexe. Mots-clés: Électromyographie, test de conduction nerveuse, Nigérians, normatif, nerf cubital.

A Cross-Sectional Comprehensive Assessment of the Profile and Burden of Non-motor Symptoms in Relation to Motor Phenotype in the Nigeria Parkinson Disease Registry Cohort.

BACKGROUND: Data on non-motor symptoms (NMS) in black Africans with Parkinson's disease (PD) are sparse. OBJECTIVE: To describe the profile of NMS in the Nigeria PD Registry (NPDR) cohort and explore the relationship between NMS and PD motor phenotype. METHODS: We conducted a cross-sectional study of the frequency and burden of NMS, based on the non-motor symptoms scale (NMSS) and the Chaudhuri method respectively in our cohort. Baseline demographics, disease characteristics (Hoehn and Yahr stage, MDS-UPDRS total score and Part III motor score), motor phenotype (based on Stebbin et al's algorithm), and levodopa equivalent daily dose (LEDD) were documented. RESULTS: Data are presented for 825 PD whose mean age at study was 63.7 ± 10.1 years, female sex-221 [26.8%] while median PD duration was 36 months. PD phenotypes included tremor-dominant 466 (56.5%), postural instability and gait disorder (PIGD) 259 (31.4%), and indeterminate 100 (12.1%). 82.6% were on treatment (median LEDD of 500 mg/24 hours). 804 (97.5%) endorsed at least 1 NMS. The median NMSS score was 26.0 while subscores for urinary and sexual function domains were significantly higher in males (P < 0.05). PIGD-PD had more frequent NMS and higher frequency of severe/very severe NMSS burden (P = 0.000 for both). Nocturia and fatigue were the most prevalent NMS overall and across motor subtypes. PIGD phenotype and total UPDRS scores were the independent determinants of NMSS scores (P = 0.000). CONCLUSION: The profile and burden of NMS, and association with motor subtype in our black African cohort is largely similar to descriptions from other populations.

The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project.

BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18-60.5 months). Young-onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per-capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub-Saharan Africa. The registry will serve as a platform for development of multipronged evidence-based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria. © 2020 International Parkinson and Movement Disorder Society.