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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
The Inuit population is often described as being protected against CVD due to their traditional dietary patterns and their unique genetic background. The objective of the present study was to examine gene–diet interaction effects on plasma lipid levels in the Inuit population. Data from the Qanuippitaa Nunavik Health Survey (n 553) were analysed via regression models which included the following: genotypes for thirty-five known polymorphisms (SNP) from twenty genes related to lipid metabolism; dietary fat intake including total fat (TotFat) and saturated fat (SatFat) estimated from a FFQ; plasma lipid levels, namely total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and TAG. The results demonstrate that allele frequencies were different in the Inuit population compared with the Caucasian population. Further, seven SNP (APOA1 − 75G/A (rs670), APOB XbAI (rs693), AGT M235T (rs699), LIPC 480C/T (rs1800588), APOA1 84T/C (rs5070), PPARG2 − 618C/G (rs10865710) and APOE 219G/T (rs405509)) in interaction with TotFat and SatFat were significantly associated with one or two plasma lipid parameters. Another four SNP (APOC3 3238C>G (rs5128), CETP I405V (rs5882), CYP1A1 A4889G (rs1048943) and ABCA1 Arg219Lys (rs2230806)) in interaction with either TotFat or SatFat intake were significantly associated with one plasma lipid variable. Further, an additive effect of these SNP in interaction with TotFat or SatFat intake was significantly associated with higher TC, LDL-C or TAG levels, as well as with lower HDL-C levels. In conclusion, the present study supports the notion that gene–diet interactions play an important role in modifying plasma lipid levels in the Inuit population.
The field of traditional chinese fiction studies is as diverse in its approaches and findings as the body of material included in the term xiaoshuo, with which the modern field imprecisely corresponds. As a term for classifying writings in early China, xiaoshuo seemingly meant “other” works that did not fit into the major category of narrative, i.e., history. In the bibliographical section of Ban Gu's (c.e. 32–92) Han shu, the Yiwen zhi, titles identified as xiaoshuo apparently were miscellaneous writings of no uniform characteristics or content. In the Han shu bibliography, xiaoshuo were classified under the zhuzi or “miscellaneous philosophers”; during the Six Dynasties period these writings were grouped in the zi or “philosophers” section of the sibu, the durable four-fold bibliographic division of all writing originated in the third century and still in use. This Han shu designation reflected the assumption that xiaoshuo are or should be generally “discursive,” even if they are of less significance than formal philosophical works. The clear discrimination between verifiable narrative works (hence historical) and fanciful (or fictitious) writings was a product of the Tang period; however, the assignment of fictional xiaoshuo to the same category as philosophy continued then as well. Like Aristotle, early Chinese bibliographers saw general truth, rather than the specific truth of history, as the operative criterion in fiction, despite the origins of many fictional narrative conventions in historiography (see K. J. DeWoskin, “Six Dynasties Chih-kuai,” esp. p. 46). Twentieth-century scholarly attempts to see the term as synonymous with the modern concept of fiction are frustrated by its original lack of specificity and the fact that patently fictitious (from the modern rationalist perspective) elements appear in all other forms of early literature, both philosophical works (as parables or the flights of imaginative fancy in Zhuang zi) and history (in fabricated conversations and fantastic events). While it may be argued that a term like “narrative,” with its coincident concern for story, discourse, and conventions (using distinctions drawn by Seymour Chatman, Coming to Terms [Ithaca: Cornell University Press, 1990], pp. 9, 83, 117, etc.), would more adequately serve to describe the range of materials modern scholars might address, because the term xiaoshuo still delineates the field for its specialists, narratives in philosophy and history are usually disallowed, and there is no general agreement on criteria by which to identify its earliest examples (see Hou Zongyi, Liuchao xiaoshuo shi, pp. 1–4, for a history of the term).