Interaction with the MAPT H1H1 Genotype Increases Dementia Risk in APOE ε4 Carriers in a Population of Southern India

Abstract

Background: This study delineates the role of the interaction of apolipoprotein E (APOE) and MAPT alleles in contributing to disease risks of dementia in a southern Indian population. Methods: A sample of 419 patients comprising Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87), frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control group (n = 138). APOE genotyping and MAPT haplotyping were performed on all study subjects. Results: Multivariate logistic regression analysis showed that variability on the APOE locus influenced the relative risk of dementia in the study population. The APOE ε4 allele increased the disease risk most significantly for AD (OR = 3.468, p < 0.0001) and MCI (OR = 2.901, p < 0.0001). The APOE ε2 allele remained protective for AD (OR = 0.205, p < 0.05). For FTD, VD, and DLB, the APOE ε4 allele was ineffectual in modulating disease risk. The MAPT H1 haplotype was not an overrepresented marker of neurodegenerative diseases. The H1H1 genotype had an additive effect in contributing to either disease risk in combination with the APOE ε4 allele or protection in combination with the APOE ε2 or ε3 allele. Conclusions: This study is a reappraisal of the strong association of APOE variability with AD in southern India when compared to other dementia groups, while the transcriptional differences between MAPT haplotypes have a limited role in Indian dementia patients.

Association between apolipoprotein E gene polymorphism and mild cognitive impairment: a meta-analysis

“…The initial search identified 721 references. Of those, 18 publications 21 – 38 with 2,004 cases and 3,705 controls were included in our meta-analysis. The study selection process was shown in Figure 1 .…”

Systematic review of genetic association studies in people with Lewy body dementia

“…MAPT encodes tau protein. Two moderate and one poor quality studies have reported significant association between MAPT H1 haplotype and DLB, but two good quality studies have not replicated this finding . Moreover, a moderate quality study has reported associations between PDD and MAPT H1 haplotype and another probably protective variant rs1467967…”

“…The APOE variants, especially its ε4 allele, are the most studied among all genetic variants in people with LBD . Apolipoprotein E (APOE) is involved in cholesterol mobilisation and redistribution during neuronal growth and injury, and it may promote β‐amyloid aggregation .…”

“…Two moderate 57,58 and one poor quality 59 studies have reported significant association between MAPT H1 F I G U R E 1 The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart [Colour figure can be viewed at wileyonlinelibrary.com] haplotype and DLB, but two good quality studies have not replicated this finding. 11,37 Moreover, a moderate quality study has reported associations between PDD and MAPT H1 haplotype and another probably protective variant rs1467967. 60 Tables 2 and 3 present other reported genetic associations of DLB and PDD, respectively.…”

Effect of Apolipoprotein E ɛ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

“…Further studies or meta-analyses should consider evaluating the interaction between APOE polymorphism and other genetic variations involving individual differences in drug efficacy or the cholinergic system. In addition to CYP2D6 single nucleotide polymorphism rs1080985, future research can evaluate the interaction with other genetic variations such as the butyrylcholinesterase genotype, phosphatidylinositol-binding clathrin assembly protein (PICALM), paraoxonase 1 gene polymorphism, CHRNA7 genotype, and MAPT genotype [24,26,[48][49][50].…”