スギモト　ケン   Ken Sugimoto   杉本　研    所属   川崎医科大学  医学部 臨床医学　総合老年医学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains.
掲載誌名	正式名：Genome research 略　 称：Genome Res ISSNコード：10889051/10889051
掲載区分	国外
巻・号・頁	17(9),pp.1319-1326
著者・共著者	Pravenec Michal, Hyakukoku Masaya, Houstek Josef, Zidek Vaclav, Landa Vladimir, Mlejnek Petr, Miksik Ivan, Dudová-Mothejzikova Kristyna, Pecina Petr, Vrbacky Marek, Drahota Zdenek, Vojtiskova Alena, Mracek Tomas, Kazdova Ludmila, Oliyarnyk Olena, Wang Jiaming, Ho Christopher, Qi Nathan, Sugimoto Ken, Kurtz Theodore
発行年月	2007/09
概要	Recently, the relationship of mitochondrial DNA (mtDNA) variants to metabolic risk factors for diabetes and other common diseases has begun to attract increasing attention. However, progress in this area has been limited because (1) the phenotypic effects of variation in the mitochondrial genome are difficult to isolate owing to confounding variation in the nuclear genome, imprinting phenomena, and environmental factors; and (2) few animal models have been available for directly investigating the effects of mtDNA variants on complex metabolic phenotypes in vivo. Substitution of different mitochondrial genomes on the same nuclear genetic background in conplastic strains provides a way to unambiguously isolate effects of the mitochondrial genome on complex traits. Here we show that conplastic strains of rats with identical nuclear genomes but divergent mitochondrial genomes that encode amino acid differences in proteins of oxidative phosphorylation exhibit differences in major metabolic risk factors for type 2 diabetes. These results (1) provide the first direct evidence linking naturally occurring variation in the mitochondrial genome, independent of variation in the nuclear genome and other confounding factors, to inherited variation in known risk factors for type 2 diabetes; and (2) establish that spontaneous variation in the mitochondrial genome per se can promote systemic metabolic disturbances relevant to the pathogenesis of common diseases.
DOI	10.1101/gr.6548207
PMID	17693571