Interaction with the MAPT H1H1 Genotype Increases Dementia Risk in APOE ε4 Carriers in a Population of Southern India
Autor: | P. S. Jairani, Pavagada S. Mathuranath, P M Aswathy, Srinivas Gopala, Joe Verghese |
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Rok vydání: | 2016 |
Předmět: |
Lewy Body Disease
Male Risk Apolipoprotein E Genotype Apolipoprotein E2 Cognitive Neuroscience Apolipoprotein E4 Population Apolipoprotein E3 India tau Proteins Disease Biology White People 03 medical and health sciences 0302 clinical medicine Alzheimer Disease mental disorders medicine Humans Dementia Cognitive Dysfunction Allele education Alleles Aged Aged 80 and over Genetics education.field_of_study 030214 geriatrics Dementia Vascular Haplotype Middle Aged medicine.disease Genotype frequency Psychiatry and Mental health Haplotypes Frontotemporal Dementia Female Geriatrics and Gerontology Biomarkers 030217 neurology & neurosurgery |
Zdroj: | Dementia and Geriatric Cognitive Disorders. 42:255-264 |
ISSN: | 1421-9824 1420-8008 |
Popis: | 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. |
Databáze: | OpenAIRE |
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