Genetic Risk Factors in Japanese Alzheimer’s Disease Patients: α1-ACT, VLDLR, and ApoE

Yamanaka, Hideharu; Kamimura, Kohei; Tanahashi, Hiroshi; Takahashi, K.; Asada, Takashi; Tabira, Takeshi

doi:10.1016/s0197-4580(98)00035-9

Cited by 33 publications

(18 citation statements)

References 16 publications

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“…Furthermore, the odds ratio for having AD was doubled in heterozygous APOE*4 individuals who also had the ACT/AA genotype and tripled in the homozygous APOE/44, ACT/AA genotype. However, our data, similar to the previously published data [9][10][11][12][13][14], did not show evidence of an association between ACT polymorphism and AD, and also failed to detect a modifying effect of this polymorphism among the carriers of the APOE*4 allele.…”

Section: Discussionsupporting

confidence: 87%

See 1 more Smart Citation

No Association between Alpha-1-Antichymotrypsin Polymorphism and Alzheimer’s Disease in Chinese

Wang

Liu²,

Liu³

et al. 1999

Neuropsychobiology

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A recent observation has shown that a common polymorphism in the α1-antichymotrypsin (ACT) confers a significant risk for Alzheimer’s disease (AD). Furthermore, the apolipoprotein E ε4 allele (APOE*4) effect associated with AD risk is modified by the ACT polymorphisms. To evaluate the role of ACT polymorphism in AD, we conducted an association study of ACT polymorphisms in Chinese AD patients and normal controls. We found that the ACT polymorphism had no effect on the development of AD either alone or in combination with the APOE*4 allele.

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Section: Discussionsupporting

confidence: 87%

“…Furthermore, they demonstrated that in individuals carrying an APOE*4 allele, the ACT-TT genotype appeared to be protective, while the ACT-AA genotype appeared to confer a two-to threefold increased risk of AD. Except for one report [8], results from recent studies do not support these findings [9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 94%

No Association between Alpha-1-Antichymotrypsin Polymorphism and Alzheimer’s Disease in Chinese

Wang

Liu²,

Liu³

et al. 1999

Neuropsychobiology

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“…We have previously reported high levels of plasma triglycerides and free fatty acids in LCR (52), which partly may be explained by low expression of cholesterollowering proteins as very low density lipoprotein receptor (VLDLr) and colony stimulating factor 1 (CSF1), as reported here and elsewhere (18,37,38,53). Administration of CSF1 has been tested as a potential therapy for hypercholesterolemia and atherosclerosis, and favorable results have been reported (50).…”

Section: Discussionsupporting

confidence: 58%

Aerobic capacity-dependent differences in cardiac gene expression

Bye

Langaas

Høydal

et al. 2008

Physiological Genomics

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Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in human, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in these animals. Left ventricle gene expression of both sedentary and exercise-trained HCR and LCR was characterized by microarray and gene ontology analysis. Out of 28,000 screened genes, 1,540 were differentially expressed between sedentary HCR and LCR. Only one gene was found differentially expressed by exercise training, but this gene had unknown name and function. Sedentary HCR expressed higher amounts of genes involved in lipid metabolism, whereas sedentary LCR expressed higher amounts of the genes involved in glucose metabolism. This suggests a switch in cardiac energy substrate utilization from normal mitochondrial fatty acid ␤-oxidation in HCR to carbohydrate metabolism in LCR, an event that often occurs in diseased hearts. LCR were also associated with pathological growth signaling and cellular stress. Hypoxic conditions seemed to be a common source for several of these observations, triggering hypoxia-induced alterations of transcription. In conclusion, inborn high vs. low aerobic capacity was associated with differences in cardiac energy substrate, growth signaling, and cellular stress. metabolic syndrome; metabolism; hypoxia; V O2max; hypertrophy ALTHOUGH MAXIMAL OXYGEN UPTAKE (V O 2max ) is statistically linked with cardiovascular mortality (23, 36), the mechanistic nature of this association is unknown and difficult to explore in humans. Specifically, it is well defined that the continuum of heart function is linearly related with the level of V O 2max (39). Within the gene-environment interactions, inheritance may account for as much as 70% of the variation in aerobic capacity in human (7). Hence, genetic predisposition and inborn aerobic capacity are likely to contribute toward cardiovascular disease and mortality.Rats with different inborn running capacities have been artificially selected over generations to generate strains with genetically determined high or low intrinsic capacity (25). The evolved strains of high capacity runners (HCR) and low capacity runners (LCR) have a 30% difference in V O 2max (17). Selecting for low running capacity also resulted in accumulation of risk factors that predispose to cardiovascular disease. That is, LCR have features of the metabolic syndrome, whereas HCR show an athletic phenotype with markedly better cardiac and vascular function relative to LCR (17, 52). These models were generated expressly for efficient and invasive evaluation of cardiometabolic disease that can lea...

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“…There was no statistically significant difference in APOE4 allele frequency between Japanese FTD patients and controls (p ! 0.0001) [23]. 1R 2F 2R 3F 3R 4F 4R 4aF 4aR 5F 5R 6F 6R 7F 7R 8F 8R 9F 9R 10F 10R 11F 11R 12F 12R 13F 13R 14F 14R CTCCTCAGAACTTATCCTCTCC CAGTGATCTGGGCCTGCTGT TCCCTTTGTGGGTTTGTTGCAG AGTGAGCACATCTCTCAGCCA CACTGCAGCGTTTACACAGGG CTGTCACAGGTCAGCTGGGG GAACTCCTCAGCAATGACATTTG GAACCAACTCCCTAAAATCTCC AGAAGGGTCCGGCCTTTCCG GGAAGCTCAGTGGCAGTGCC TGGCTTTCTGTGAACAGTGAAAT CATAAAGCACAGCTTCTCTGTAA AGTTTGTTTCCCTCCTCCATGT CACATTTGCAAACCACTGC GGGTCACCCCAGTCTTAGCC AGCTTCAGCTTCCTCTAAGATTCAAG GAAGGACTCATTAAGGCCCTGT CTGCTCCCAGCGAGTAGGCT TCGAGTCCTGGCTTCACTCC CACGCTCAACCGCGCACC CGAGCAAGCAGCGGGTCCA GTACGACTCACACCACTTCCT CTCTCCTCCTCTCTCCCATCTCC TCACCAGGACTCCTCCACCC CAGAACCACAGAAGATGATGGC CCAACCACCCTACCCCCT ACTTCATCTCACCCTCCCTC CCTCTCCTTCTCCCTCTTCTAC GCACTTCGATGATGACCTCC Two pathogenic mutations were found in Japanese familial FTD and DNA polymorphisms were found in a Polish sporadic case of FTD.…”

Section: Resultsmentioning

confidence: 99%

Genetic Analysis in Patients with Familial and Sporadic Frontotemporal Dementia: Two Tau Mutations in Only Familial Cases and No Association with Apolipoprotein ε4

Kowalska

Asada

Arima

et al. 2001

Dement Geriatr Cogn Disord

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We screened for tau gene mutations among 24 Japanese (6 familial and 18 sporadic cases) and 4 Polish patients with frontotemporal dementia (FTD) using PCR-SSCP analysis followed by DNA sequencing. We identified 2 missense mutations in exon 10: N279K and P301L in 2 Japanese patients with familial FTD. Additionally 3 DNA polymorphisms: 2 known (3′ exon 3 + 9, A → G and exon 7, codon 176, G → A) and 1 new (exon 8, codon 185, T → C) were identified in 1 Polish patient. Tau mutations were not found in subjects with a negative family history suggesting that tau mutations do not account for most sporadic cases of FTD. We also found no association of apolipoprotein E4 allele with FTD.

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Genetic Risk Factors in Japanese Alzheimer’s Disease Patients: α1-ACT, VLDLR, and ApoE

Cited by 33 publications

References 16 publications

No Association between Alpha-1-Antichymotrypsin Polymorphism and Alzheimer’s Disease in Chinese

No Association between Alpha-1-Antichymotrypsin Polymorphism and Alzheimer’s Disease in Chinese

Aerobic capacity-dependent differences in cardiac gene expression

Genetic Analysis in Patients with Familial and Sporadic Frontotemporal Dementia: Two Tau Mutations in Only Familial Cases and No Association with Apolipoprotein ε4

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