Genetic Association of GHR and IGF-1 with Facial Growth

Objectives: Progress in understanding how genetic variation is associated with differences in facial growth during puberty would help in studies of growth prediction and orthodontic treatment planning. The specific aim was to determine whether genetic variations in the GHR gene (rs2972408, rs4130114, rs6180) and/or the IGF-1 gene (rs10735380, rs1520220 and rs2946834) were associated with differences in facial growth rates.
Methods: Subjects were chosen from an IRB approved database of approximately 1,500 patients with pre and post orthodontic radiographs, examination notes, and genomic DNA. Cervical Vertebral Maturation Stages were evaluated by three independent orthodontists and agreement of at least two designated the patient’s stage. Subjects with an initial CVMS of 3 were included in the study. Initial and final cephalometric radiographs were traced by one individual. The differences in initial and final linear and angular measurements were annualized over the treatment period to normalize for differences in treatment time. A stepwise multiple regression (JMP® GENOMICS, SAS Institute Inc, Cary, NC) was performed to determine association between any of the genetic variations and any facial measurements.
Results: Genetic variation in rs6180 was associated with changes in ANB (p = .008), WITS (p = .005), and mandibular length as measured by Co-Gn (p = .01). Genetic variation in rs2946834 was associated with changes in midface length as measured by Co-ANS (p = .04). Sex was found to be significant for a number of variables including: Co-ANS, LPDH, UPDH, LAFH, Co-Gn, Ar-Go, S-Go. No associations were identified for SNPs rs2972408, rs4130114, rs10735380, or rs1520220 and the facial growth parameters measured.
Conclusions: Genetic variation in the GHR gene at rs6180 may explain differences in facial growth; especially in the anterior-posterior dimension.