Investigation on pathogenesis and therapy of COPD with phenotypes of Marfan syndrome, especially on its relation to ECM malformation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461174
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nippon Medical School
• Principal Investigator: Kida Kozui 日本医科大学, 医学部, 教授 (90142645)
• Co-Investigator(Kenkyū-buntansha): Arai Tomio 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (20232019) ; Betsuyaku Tomoko 慶應義塾大学, 医学部(信濃町), 教授 (60333605) ; Ishii Takeo 日本医科大学, 医学部, 講師 (90445750)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 慢性閉塞性肺疾患 / 遺伝子多型 / ECM / マルファン症候群

Outline of Final Research Achievements

COPD with thracic aneurysm is similar to Marfan syndrome from the clinical point of view, and both diseases could have a common pathogenesis through extracellular (ECM) malformation. Thus, we hypothesized that ECM-related genes have critical roles in pathogenesis of emphysema and their genetic variations (single nucleotide polymorphisms (SNPs)) are associated with emphysema severity in human.Two populations were studied: population A comprised 574 smokers including 352 COPD , and population B comprised 329 smokers including 258 COPD . In population A. A G allele at SNP rs1051303 (one of the coding SNPs of LTBP4) was positively correlated with the low-attenuation area (LAA%) in the upper lung (p = 0.029) in population A, and this relationship was validated in population B in one-sided test (p = 0.038). LTBP4 might have a critical role in pathogenesis of emphysema in human. The pathogenetic mechanism related to LTBP4 remains to be elucidated.

Free Research Field

呼吸器内科学