Moreover, the 4q31 locus, containing the Hedgehog interacting protein (HHIP) gene, which mediates epithelial mesenchymal transformation (EMT) due to smoking, has been reported to have a protective effect on both LC and COPD, particularly rs1489759 and rs2202507 single-nucleotide polymorphisms (SNPs). This evidence concerns the gene HHIP and chronic obstructive pulmonary disease.