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The association of LAMB1 polymorphism and expression changes with the risk of coal workers' pneumoconiosis
Xiaoming Ji1, Baiqun Wu1, Ruhui Han1
1Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
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.
