Molecular mechanism underlying the association between Y2 receptor SNPs and HDL metabolism

2015 Fiscal Year Final Research Report

• Project/Area Number: 25504009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrated Nutrition Science
• Research Institution: University of Hyogo
• Principal Investigator: KAJI Hidesuke 兵庫県立大学, 看護学部, 教授 (90224401)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Y2 receptor (Y2R) / SNPs / HDL-cholesterol / HepG2 / BIIE0246 / マイクロアレイ / バイオインフォ-マティクス

Outline of Final Research Achievements

We have previously reported the association between Y2R gene SNPs and plasma HDL-C levels. The present study was undertaken to clarify the mechanism of this association. Reporter with Y2R gene containing these SNPs were transiently transfected to various cell lines. Human liver cell HepG2 showed transcriptional activity of Y2R gene with the SNPs associated with lower but not higher plasma HDL-C.
HepG2 contained DNA with these SNPs, so we tested the effect of Y2R antagonist BIIE0246 on gene expression. Microarray analysis revealed BIIE0246-induced up- and down-regulation (>1.5) of 743 and 492 transcripts,respectively. Up-regulated genes were included in chylomicron remodeling and negative regulation of cholesterol/sterol transport, and also included in the pathway of HDL metabolism. Down-regulated genes were included in the pathway of SREBP signaling. These results suggest that Y2R antagonist may be a drug candidate for dyslipidemia in subjects with the specified Y2R SNPs.

Free Research Field

内分泌代謝学