Association of Polymorphic Loci of Long Noncoding RNA Genes (H19, MEG3, MALAT1, LINC00305, LINC00261, LINC02227, and CDKN2B-AS1) with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease resulting from dynamic, cumulative gene-environment interactions that cause lung tissue injury, alteration of its normal function, and acceleration of cellular senescence. Long noncoding RNAs (lncRNAs) function as critical epigenetic regulators of various aspects of cellular senescence. The objective of the present study is to identify the association between polymorphic variants of H19 (rs3741219), MEG3 (rs7158663), MALAT1 (rs619586), LINC00305 (rs2850711), LINC00261 (rs6048205), CDKN2B-AS1 (rs4977574), and LINC02227 (rs2149954) lncRNAs genes with COPD. DNA samples from COPD patients (N = 703) and healthy individuals (N = 655) were studied in this study and polymorphic loci were analyzed by real-time PCR. Association with COPD was established with H19 (rs3741219), MEG3 (rs7158663), LINC02227 (rs2149954), MALAT1 (rs619586) and CDKN2B-AS1 (rs4977574). Polygenic analysis has made it possible to identify informative gene-gene combinations that include polymorphic variants of the studied lncRNAs genes and genes encoding molecules of signaling cascades associated with cellular senescence and apoptosis. Multiple regression and ROC analysis revealed a COPD risk predictive model, which included gene-gene combinations of lncRNAs genes and smoking index (P = 4.01 x 10(-48), AUC = 0.87).