Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (S...

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Autores principales:	Koji Hayashi, Moeko Noguchi-Shinohara, Takehiro Sato, Kazuyoshi Hosomichi, Takayuki Kannon, Chiemi Abe, Chiaki Domoto, Sohshi Yuki-Nozaki, Ayaka Mori, Mai Horimoto, Masami Yokogawa, Kenji Sakai, Kazuo Iwasa, Kiyonobu Komai, Mai Ishimiya, Hiroyuki Nakamura, Natsuko Ishida, Yukio Suga, Junko Ishizaki, Akihito Ishigami, Atsushi Tajima, Masahito Yamada
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fd9732df1c6744229aa08b2ca9353a01
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spelling	oai:doaj.org-article:fd9732df1c6744229aa08b2ca9353a012021-11-25T06:10:53ZEffects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study1932-6203https://doaj.org/article/fd9732df1c6744229aa08b2ca9353a012021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592483/?tool=EBIhttps://doaj.org/toc/1932-6203Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case–control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05–3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05–5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58–6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.Koji HayashiMoeko Noguchi-ShinoharaTakehiro SatoKazuyoshi HosomichiTakayuki KannonChiemi AbeChiaki DomotoSohshi Yuki-NozakiAyaka MoriMai HorimotoMasami YokogawaKenji SakaiKazuo IwasaKiyonobu KomaiMai IshimiyaHiroyuki NakamuraNatsuko IshidaYukio SugaJunko IshizakiAkihito IshigamiAtsushi TajimaMasahito YamadaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Koji Hayashi Moeko Noguchi-Shinohara Takehiro Sato Kazuyoshi Hosomichi Takayuki Kannon Chiemi Abe Chiaki Domoto Sohshi Yuki-Nozaki Ayaka Mori Mai Horimoto Masami Yokogawa Kenji Sakai Kazuo Iwasa Kiyonobu Komai Mai Ishimiya Hiroyuki Nakamura Natsuko Ishida Yukio Suga Junko Ishizaki Akihito Ishigami Atsushi Tajima Masahito Yamada Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study
description	Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case–control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05–3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05–5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58–6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.
format	article
author	Koji Hayashi Moeko Noguchi-Shinohara Takehiro Sato Kazuyoshi Hosomichi Takayuki Kannon Chiemi Abe Chiaki Domoto Sohshi Yuki-Nozaki Ayaka Mori Mai Horimoto Masami Yokogawa Kenji Sakai Kazuo Iwasa Kiyonobu Komai Mai Ishimiya Hiroyuki Nakamura Natsuko Ishida Yukio Suga Junko Ishizaki Akihito Ishigami Atsushi Tajima Masahito Yamada
author_facet	Koji Hayashi Moeko Noguchi-Shinohara Takehiro Sato Kazuyoshi Hosomichi Takayuki Kannon Chiemi Abe Chiaki Domoto Sohshi Yuki-Nozaki Ayaka Mori Mai Horimoto Masami Yokogawa Kenji Sakai Kazuo Iwasa Kiyonobu Komai Mai Ishimiya Hiroyuki Nakamura Natsuko Ishida Yukio Suga Junko Ishizaki Akihito Ishigami Atsushi Tajima Masahito Yamada
author_sort	Koji Hayashi
title	Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study
title_short	Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study
title_full	Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study
title_fullStr	Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study
title_full_unstemmed	Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study
title_sort	effects of functional variants of vitamin c transporter genes on apolipoprotein e e4-associated risk of cognitive decline: the nakajima study
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/fd9732df1c6744229aa08b2ca9353a01
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Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study

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