Effect of rs4719839 polymorphism on risk of ventilator-associated pneumonia, expression of microRNA-148 and autophagy-related 16-like 1 (ATG16L1).

Abstract

MiR‐148 is a negative regulator of autophagy 16‐like 1 (ATG16L1), a gene implicated in the pathogenesis of ventilator‐associated pneumonia (VAP). Therefore, the role of miR‐148 polymorphism in the pathogenesis of VAP was studied here. The expression of miR‐148, ATG16L1, Beclin‐I, LC3‐II, TNF‐α and IL‐6 in serum and peripheral blood mononuclear cells (PBMCs) of VAP patients was detected to study their relationship in the pathogenesis of VAP. Chronic obstructive pulmonary disease patients carrying the AA/AG genotypes of miR‐148 rs4719839 single nucleotide polymorphism (SNP) were more prone to VAP due to the higher expression of miR‐148, TNF‐α and IL‐6 along with suppressed expression of ATG16L1, Beclin‐I and LC3‐II in their serum and PBMCs. Transfection of miR‐148 mimics to primary PBMCs genotyped as GG and AA decreased the expression of ATG16L1, Beclin‐I and LC3‐II. Finally, cells carrying the AA genotype of rs4719839 SNP were more sensitive to the role of LPS stimulation in suppressing ATG16L1, Beclin‐I and LC3‐II expression while activating TNF‐α and IL‐6 expression. Our work presented detailed evidence, suggesting that the rs4719839 polymorphism can affect the risk of VAP.