Cellular function analysis of a novel psoriatic pathogenesis gene, PTRF / Cavin-1, and its involvement in psoriatic pathology

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08678
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Tsuda Hidetoshi 自治医科大学, 医学部, 助教 (30414923)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 乾癬 / Psoriasis / SNP / GWAS / PTRF / Cavin1 / 遺伝子発現

Outline of Final Research Achievements

Recently, GWAS analysis has newly reported SNPs that are strongly associated with psoriasis pathology, and it has been reported that SNPs in the gene PTRF/Cavin1 are deeply associated with psoriasis pathology. However, this SNP is located on an intron of this gene, and its effect on gene function is unknown. Therefore, we decided to introduce SNPs into HaCaT cells by genome editing and examine whether they would affect the expression and function of the PTRF gene. Although we obtained some clones with deletions in the genome, we were unable to obtain clones in which the desired SNP could be introduced. Gene expression analysis was performed on clones with deletions near some SNPs, but no differences were found compared to control cells.

Free Research Field

分子細胞生物学、遺伝子工学

Academic Significance and Societal Importance of the Research Achievements

疾患における遺伝的背景にはまだまだ不明なことが多い。また、GWAS解析にて病態との関連が指摘されるSNPは数多く報告されているが、多くの場合はintronに報告されている。exon上にSNPがあり、アミノ酸変異を伴う変異であれば比較的容易に判断できるが、intron上にある場合、一見して遺伝子機能に影響するか否か判断は出来ない。今回この問題に対して研究を行ったが、明らかな違いを示すことは出来なかった。今後更にゲノム編集技術が進歩し、より簡便にゲノム編集を行えるようになれば、新たな遺伝子機能への影響を明らかにすることが可能となると考えている。