Dataset Information

Interaction between Apolipoprotein E and Butyrylcholinesterase Genes on Risk of Alzheimer's Disease in a Prospective Cohort Study.

ABSTRACT:

Background

An epistatic interaction between the ɛ4 allele of apolipoprotein E (APOEɛ4) gene and the K-variant of butyrylcholinesterase (BCHE-K) genes has been previously reported to increase risk of Alzheimer's disease (AD). However, these observations were largely from case-control studies with small sample sizes.

Objective

To examine the interaction between APOEɛ4 and BCHE-K on: 1) the risk of incident AD and 2) rates of change in brain volumes and cognitive performance during the preclinical stages of AD in a prospective cohort study.

Methods

The study sample for survival analysis included 691 Caucasian participants (age at baseline, 58.4±9.9 years; follow-up time,16.9±9.7 years) from the Baltimore Longitudinal Study of Aging. The neuroimaging sample included 302 participants with 1,388 magnetic resonance imaging (MRI) scans. Cognitive performance was assessed in 703 participants over 4,908 visits.

Results

A total of 122 diagnoses (79 AD, 43 mild cognitive impairment [MCI]) were identified. Participants with both APOEɛ4 and BCHE-K variants had a 3.7-fold greater risk of AD (Hazard ratio [HR] 95% CI=1.99-6.89, p < 0.001) compared to non-carriers of both genes (APOE ɛ4 x BCHE-K interaction p = 0.025). There was no APOE ɛ4-BCHE-K interaction effect on rate of cognitive decline and brain atrophy.

Conclusion

The APOE and BCHE genes interact to influence risk of incident AD/MCI but not rates of brain atrophy and decline in cognitive performance before onset of cognitive impairment. This may suggest the epistatic interaction between APOE ɛ4 and BCHE-K on AD risk is disease stage-dependent.

SUBMITTER: Chuang YF

PROVIDER: S-EPMC10845166 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Interaction between Apolipoprotein E and Butyrylcholinesterase Genes on Risk of Alzheimer's Disease in a Prospective Cohort Study.

Chuang Yi-Fang YF Varma Vijay V An Yang Y Tanaka Toshiko T Davatzikos Christos C Resnick Susan M SM Thambisetty Madhav M

Journal of Alzheimer's disease : JAD 20200101 2

<h4>Background</h4>An epistatic interaction between the ɛ4 allele of apolipoprotein E (APOEɛ4) gene and the K-variant of butyrylcholinesterase (BCHE-K) genes has been previously reported to increase risk of Alzheimer's disease (AD). However, these observations were largely from case-control studies with small sample sizes.<h4>Objective</h4>To examine the interaction between APOEɛ4 and BCHE-K on: 1) the risk of incident AD and 2) rates of change in brain volumes and cognitive performance during t ...[more]

PMID: 32250307

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Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66Â·1% (95% CI 63Â·2â68Â·9) and a specificity of 80Â·6% (79Â·2â82Â·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0Â·018 for RNA sequencing and p=0Â·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0Â·0001 by qRT-PCR) with a sensitivity of 53Â·7% (42Â·6â64Â·3) and a specificity of 82Â·8% (76Â·7â86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. In this prospective cohort study, we followed up healthy, South African adolescents aged 12â18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.

Dataset Information

Interaction between Apolipoprotein E and Butyrylcholinesterase Genes on Risk of Alzheimer's Disease in a Prospective Cohort Study.

Background

Objective

Methods

Results

Conclusion

Publications

Interaction between Apolipoprotein E and Butyrylcholinesterase Genes on Risk of Alzheimer's Disease in a Prospective Cohort Study.

Similar Datasets

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