Increase of serum uric acid levels associated with APOE ε2 haplotype: a clinico-genetic investigation and in vivo approach View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-09-16

AUTHORS

Masatsune Ogura, Yu Toyoda, Masayuki Sakiyama, Yusuke Kawamura, Akiyoshi Nakayama, Yoshihide Yamanashi, Tappei Takada, Seiko Shimizu, Toshihide Higashino, Mayuko Nakajima, Mariko Naito, Asahi Hishida, Sayo Kawai, Rieko Okada, Makoto Sasaki, Makoto Ayaori, Hiroshi Suzuki, Koki Takata, Katsunori Ikewaki, Mariko Harada-Shiba, Nariyoshi Shinomiya, Hirotaka Matsuo

ABSTRACT

Elevated serum uric acid (SUA)—hyperuricemia—is caused by overproduction of urate or by its decreased renal and/or intestinal excretion. This disease, which is increasing in prevalence worldwide, is associated with both gout and metabolic diseases. Several studies have reported relationships between apolipoprotein E (APOE) haplotypes and SUA levels in humans; however, their results remain inconsistent. This prompted us to investigate the relationship between APOE polymorphisms and SUA levels. Our subjects were 5,272 Japanese men, premenopausal women, and postmenopausal women. Multiple linear regression analyses revealed the ε2 haplotype of APOE to be independently associated with higher SUA in men (N = 1,726) and postmenopausal women (N = 1,753), but not in premenopausal women (N = 1,793). In contrast, the ε4 haplotype was little related to SUA levels in each group. Moreover, to examine the effect of Apoe deficiency on SUA levels, we conducted animal experiments using Apoe knockout mice, which mimics ε2/ε2 carriers. We found that SUA levels in Apoe knockout mice were significantly higher than those in wild-type mice, which is consistent with the SUA-raising effect of the ε2 haplotype observed in our clinico-genetic analyses. Further analyses suggested that renal rather than intestinal underexcretion of urate could be involved in Apoe deficiency-related SUA increase. In conclusion, we successfully demonstrated that the ε2 haplotype, but not the ε4 haplotype, increases SUA levels. These findings will improve our understanding of genetic factors affecting SUA levels. More... »

PAGES

1727-1733

References to SciGraph publications

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  • Journal

    TITLE

    Human Cell

    ISSUE

    6

    VOLUME

    34

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s13577-021-00609-w

    DOI

    http://dx.doi.org/10.1007/s13577-021-00609-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1141165720

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34532841


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