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2018 Fiscal Year Final Research Report

Elucidation of medical-genetic and patho-physiological involvement of DNase family in myocardial infarction and cancer

Research Project

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Project/Area Number 16H05272
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionUniversity of Fukui

Principal Investigator

YASUDA Toshihiro  福井大学, 学術研究院医学系部門, 教授 (80175645)

Research Collaborator IIDA Reiko  
UEKI Misuzu  
KOMINATO Yoshihiko  
TAKESHITA Haruo  
KOBAYASHI Motohiro  
KAWAI Yasuyuki  
Project Period (FY) 2016-04-01 – 2019-03-31
KeywordsDNase / 遺伝的多型 / 一塩基多型 / 心筋梗塞 / 自己免疫疾患 / 遺伝的リスクファクター / 遺伝的多様性
Outline of Final Research Achievements

We could demonstrate that; (1) Total 42 genetic variants producing a loss-of-function could be identified in DNASE1. (2) In DNase 1-like 3 and DNase II genes, which have assumed to be involved in rheumatoid arthritis, 4 and 5 non-synonymous SNPs abolishing the activity, respectively, were found. Furthermore, the synonymous SNPs in the latter exhibited a significant association with rheumatoid arthritis in the Japanese populations. (3) DNase I-like 2 has been assumed to play a role in the etiology of parakeratosis through incomplete degradation of DNA in the epidermis. In DNASE1L2, 32 missense SNPs and 19 SNPs originating from frameshift/ nonsense variants resulted in loss of function of the enzyme. (4) Almost all the variants producing a loss-of-function exhibited extremely low genetic heterogeneity. (5) Each of the minor alleles for these genetic variants may serve as one of genetic risk factors for various diseases, even though they lack a worldwide genetic distribution.

Free Research Field

法医学、病態遺伝生化学、酵素学

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患や心筋梗塞などに関与するDNase I遺伝子では42個の、関節リウマチに関与するDNase 1-like 3およびDNase II遺伝子ではそれぞれ4及び5個の、尋常性乾癬における不全角化病変異に係るDNase 1-like 2遺伝子では51個の不活性な酵素を産生するgenetic variantsを同定した。これらはin vivo DNase活性を減弱させるものであり、それら疾患のリスクファクターとなる。本研究の結果はDNase familyが自己免疫疾患などの遺伝的背景の一部となることの確証をもたらすものであり、もって、オーダーメード医療の推進に寄与できる。

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Published: 2020-03-30  

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