To present current views that are pertinent to the investigation of the genetic etiology of Class III
malocclusion. Class III
malocclusion is thought to be a polygenic disorder that results from an interaction between susceptibility genes and environmental factors. However, research on family pedigrees has indicated that Class III
malocclusion might also be a monogenic dominant phenotype. Recent studies have reported that genes that encode specific
growth factors or other signaling molecules are involved in condylar growth under mechanical strain. These genes, which include Indian hedgehog homolog (IHH),
parathyroid-hormone like
hormone (PTHLH),
insulin-like growth factor-1 (IGF-1), and
vascular endothelial growth factor (
VEGF), and variations in their levels of expression play an important role in the etiology of Class III
malocclusion. In addition, genome-wide scans have revealed chromosomal loci that are associated with Class III
malocclusion. It is likely that chromosomal loci 1p36, 12q23, and 12q13 harbor genes that confer susceptibility to Class III
malocclusion. In a case-control association study, we identified
erythrocyte membrane protein band 4.1 (EPB41) to be a new positional candidate gene that might be involved in susceptibility to mandibular
prognathism. Most of the earlier studies on the genetic etiology of Class III
malocclusion have focused on the patterns of inheritance of this phenotype. Recent investigations have focused on understanding the genetic variables that affect Class III
malocclusion and might provide new approaches to uncovering the genetic etiology of this phenotype.