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The apolipoprotein E4 (APOE ε4) allele has attracted attention as an age-related genetic factor, both in neurology and gerontology. To understand the effects of the APOE ε4 allele on mortality in elderly individuals, we combined Japanese prospective cohort studies comprising 535 very old individuals (85-99 years of age) and 930 centenarians (over 100 years of age) and analyzed the association between mortality rates and candidate factors, including the APOE ε4 allele. APOE genotyping revealed an inverse correlation between the APOE ε4 allele carrier rate and age. Additionally, APOE ε4 allele carrier rate in centenarian men was significantly lower than that in centenarian women. The association analysis between APOE ε4 allele carriers and all-cause mortality indicated that APOE ε4 carriers showed significantly higher mortality rates than the APOE ε4 non-carriers among men in the very old group. Further analysis using Cox proportional hazard models indicated that cause-specific mortalities, including pneumonia and severe dementia, were associated with APOE ε4 carriers. These findings indicate that the APOE ε4 allele shows phenotypic male-specific adverse effects in the very old, which would explain the high mortality rate observed in this group, resulting in a low APOE ε4 allele carrier rate in centenarian men.
This article was published in the following journal.
Name: The journals of gerontology. Series A, Biological sciences and medical sciences
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A species of FLAVIVIRUS, one of the Japanese encephalitis virus group (ENCEPHALITIS VIRUSES, JAPANESE), found in Australia and New Guinea. It causes a fulminating viremia resembling Japanese encephalitis (ENCEPHALITIS, JAPANESE).
A species of FLAVIVIRUS, one of the Japanese encephalitis virus group (ENCEPHALITIS VIRUSES, JAPANESE), which is the etiological agent of Japanese encephalitis found in Asia, southeast Asia, and the Indian subcontinent.
A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.
A 34-kDa glycosylated protein. A major and most common isoform of apolipoprotein E. Therefore, it is also known as apolipoprotein E (ApoE). In human, Apo E3 is a 299-amino acid protein with a cysteine at the 112 and an arginine at the 158 position. It is involved with the transport of TRIGLYCERIDES; PHOSPHOLIPIDS; CHOLESTEROL; and CHOLESTERYL ESTERS in and out of the cells.
The second most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. It has a high lipid affinity and is known to displace APOLIPOPROTEIN A-I from HDL particles and generates a stable HDL complex. ApoA-II can modulate the activation of LECITHIN CHOLESTEROL ACYLTRANSFERASE in the presence of APOLIPOPROTEIN A-I, thus affecting HDL metabolism.
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