Interaction with the MAPT H1H1 Genotype Increases Dementia Risk in APOE epsilon 4 Carriers in a Population of Southern India
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Date
2016
Journal Title
Journal ISSN
Volume Title
Publisher
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS
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 e4 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 epsilon 2 allele remained protective for AD (OR = 0.205, p < 0.05). For FTD, VD, and DLB, the APOE epsilon 4 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 epsilon 4 allele or protection in combination with the APOE epsilon 2 or epsilon 3 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. (C) 2016 S. Karger AG, Basel
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Keywords
Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry
Citation
42 ,42891;255-264