The search and prospective follow-up study of genetic predisposition and environmental factors of ectopic fat accumulation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka University (2015); Kyoto University (2013-2014)
• Principal Investigator: Hotta Kikuko 大阪大学, 医学部附属病院, 講師 (30360639)
• Co-Investigator(Kenkyū-buntansha): KITAMOAO Takuya 京都大学, 大学院医学研究科, 特定技術職員 (10456882) ; KITAMOAO Aya 京都大学, 大学院医学研究科, 教務補佐 (30381627)
• Co-Investigator(Renkei-kenkyūsha): YONEDA Masato 横浜市立大学, 大学病院, 助教 (10423831) ; HYOGO Hideyuki 広島大学, 学内共同利用施設等, 助教 (40397930)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 非アルコール性脂肪肝疾患 / 内臓脂肪蓄積 / 次世代シークエンサー / エピゲノム / 遺伝子多型 / メタボリックシンドローム

Outline of Final Research Achievements

Genome-wide association study (GWAS) was performed and revealed that SNP rs738409 in the PNPLA3 plays a key role in the development of non-alcoholic fatty liver disease (NAFLD). We performed targeted next-generation sequence analysis and fine mapping of the linkage disequilibrium block containing PNPLA3 rs738409 and found that polymorphisms in the encoding the SAMM50 and PARVB are associated with the development and progression of NAFLD as well. We performed targeted-bisulfite sequencing and found that hypomethylation of CpG26 and hypermethylation of CpG99 may contribute to the severity of fibrosis in NAFLD. The levels of CpG99 methylation and PNPLA3 mRNA were affected by the rs738409 genotype.

Free Research Field

遺伝学