Premium
The association of LAMB1 polymorphism and expression changes with the risk of coal workers' pneumoconiosis
Author(s) -
Ji Xiaoming,
Wu Baiqun,
Han Ruhui,
Yang Jingjin,
Ayaaba Esther,
Wang Ting,
Han Lei,
Ni Chunhui
Publication year - 2017
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22431
Subject(s) - pneumoconiosis , biology , pathology , medicine
Background Pneumoconiosis is a serious occupational disease worldwide, which is characterized by irreversible and diffuse lung fibrotic lesions. Laminin beta 1(LAMB1) is widely expressed in tissues and it is crucial for both lung morphogenesis and physiological function. In this study, we explored the association between LAMB1 rs4320486 and risk of pneumoconiosis in a Chinese population, as well as its mechanisms. Methods In this case‐control study, 600 CWP patients and 605 controls were genotyped for the LAMB1 rs4320486 polymorphism using TaqMan methods. Luciferase reporter assay was used to assess the LAMB1 transcriptional activities. The protein levels in cells and tissues were detected by western blot, and mRNA levels were determined by qRT‐PCR. Results Logistic regression analysis revealed that individuals with LAMB1 rs4320486 CT/TT genotypes had a significantly decreased risk of CWP (adjusted OR = 0.78, 95%CI = 0.64‐0.94), compared with individuals with CC genotypes. Luciferase assays showed that the LAMB1 rs4320486(C > T) substitution could decrease the expression of LAMB1 . Compared with normal groups, mRNA levels of LAMB1 were up‐regulated in lung tissues of patients with pulmonary fibrosis. Additionally, expressions of LAMB1 and α‐SMA were enhanced progressively, along with the development of lung fibrosis, while E‐cadherin decreased. Conclusions In this study, the functional LAMB1 rs4320486 mutation was associated with a decreased risk of CWP in a Chinese population, probably owing to the reduced activity of LAMB1 transcription. LAMB1 expression was increased in the progress of lung fibrosis, which suggests that LAMB1 may affect the initiation and progression of pneumoconiosis, or serve as a potential biomarker of pneumoconiosis for diagnosis and genetic susceptibility.