ACTN3 and ENPP1 Contribute to Sagital Craniofacial Differences in Humans

Objectives: ACTN3 encodes α-actinin-3, a sarcomeric myofibril anchor protein expressed in fast contracting type II skeletal muscle fibers. When Actn3 is knocked down in mice, Enpp1 expression, which regulates osteoblast/osteoclast activity, is altered. The goal of this project was testing for association between genetic variants in ACTN3 and ENPP1 and sagital malocclusion definitions in humans.
Methods: Seven single nucleotide polymorphisms (three in ACTN3 and four in ENPP1) were studied in 150 individuals (53 Class I, 35 Class II, and 62 Class III) from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository. Skeletal diagnosis included cephalometric values indicative of Class I, II, and III such as ANB values, Witts appraisal, and A-B plane. Additional criteria included overjet and visual facial profiles as determined by the subject’s clinical evaluation. Subjects with Class I malocclusion without jaw deformations were used as reference for statistical comparisons. Race, sex, and age were recorded for all subjects. Genetic markers were tested by polymerase chain reaction using TaqMan chemistry. Chi-square and Fisher’s exact tests were used to determine overrepresentation of a marker allele with alpha of 0.05.
Results: An association was unveiled between markers in ACTN3 (rs1671064, p=0.01; rs1815739, p=0.01; rs678397, p=0.009) and Class II malocclusion. Also, markers in ENPP1 (rs9373000, p=0.04; rs6569759, p=0.04) were associated with Class III.
Conclusions: We provide evidence that ACTN3 and ENPP1 contribute to sagital craniofacial differences in humans.