MAPTallele and haplotype frequencies in Nigerian Africans: population distribution and association with Parkinson’s disease risk and age at onset

Abstract

AbstractBackgroundThe 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 onMAPThaplotype frequencies in the general population and association studies exploring the role ofMAPThaplotypes in conferring PD risk in black Africans are lacking.ObjectivesTo determine the frequencies ofMAPThaplotypes and explore the role of the H1 haplotype as a risk factor for PD risk and age at onset in Nigerian Africans.MethodsThe haplotype and genotype frequencies ofMAPTrs1052553 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.ResultsThe frequency of the mainMAPTH1 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 frequentMAPTgenotype 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).ConclusionsOur findings support previous studies that report a low frequency of theMAPTH2 haplotype in black ancestry Africans, but document its occurrence in the Nigerian population (2.1%). In this cohort of black Africans with PD, theMAPTH1 haplotype was not associated with an increased risk or age at onset of PD.