COL4A4 and keratoconus: Moreover, subjects with a family history of KC are more susceptible to this disorder.[8] Using family-based linkage, several case–control studies have determined various genes that increase the odds of KC development.[9] The gene candidates for KC include LOX,[10]VSX1,[11]GPX-1,[12]TGF-β1,[13]COL4A3 and COL4A4[14] (polymorphism or mutation), and TIMP-1,[15]MMP-2, MMP-9[16] (gene expression).