الفهرس | Only 14 pages are availabe for public view |
Abstract Interstitial lung diseases (ILDs) encompasses many chronic lung disorders with variable degrees of pulmonary fibrosis. A genome-wide association study (GWAS) followed by fine-mapping identified a novel singlenucleotide polymorphism (SNP; rs641738) in the membrane bound O-acyltransferase domain containing 7 gene (MBOAT7), to be associated with alcoholic cirrhosis. We explored the association of MBOAT7 rs641738 variants with ILD in an Egyptian patient. Furthermore, we investigated MBOAT7 and its proposed TLR4/NF-kB pathway mRNA expression pattern at human peripheral blood mononuclear cells (PBMCs) and micetissue level of bleomycin (BLM)-induced pulmonary fibrosis model. At afunctional level, rs641738-C associated with MBOAT7 transcript andassociated with TLR4 and its downstream markers, implying a role in lunginflammation. Importantly, expression of TLR4 and its downstream markersside by side with the measured profibrogenic and inflammatory cytokineswere markedly affected in association with MBOAT7 mRNA expression.We conclude that the MBOAT7 rs641738 polymorphism is a novel riskvariant for lung inflammation in ILD, and thereby for lung fibrosis and its association with TLR4/NF-kB pathway open the door for future studies thatcan improve the lifestyle of ILD patients. |