Analysis of the Relationship Between Growth Hormone Receptor Polymorphism rs6180 and Craniofacial Morphological Changes Associated with Herbst Appliance Therapy

Abstract

Craniofacial growth results from both environmental and genetic factors over time. It would be exciting to isolate genetic factors that influence treatment responses from patients undergoing orthodontic treatment. Genetic genotyping and analysis of orthodontic patients is a new technologic advancement. The aim of this retrospective study is to examine the relationship of a specific single nucleotide polymorphism (SNP), rs6180, of the Growth Hormone Receptor (GHR) gene with various craniofacial length parameters in patients who have received Herbst appliance therapy as part of orthodontic treatment.

An initial lateral cephalometric radiograph was taken along with two buccal cheek swabs. The cells obtained have undergone DNA isolation with the Puregene method in microcentrifuge tubes (Gentra Systems, Minneapolis, MN). Upon termination of functional appliance therapy (post-Herbst), a final lateral cephalometric radiograph was taken. To analyze the genetic polymorphism and determine genotype, polymerase chain reaction (PCR) and allelic discrimination were done using the 7000 Sequence Detection System (Applied Biosystems).

Lateral cephalometric radiographs (initial, post-Herbst) of 25 patients were digitized and measured using the Dolphin Imaging program. Cephalometric measurements (S-N, S-A, Co-Go, Go-Gn, Ar-Gn, Go-Gn) were used to identify mandibular and craniofacial morphologic changes. Changes in Z-scores based on standards from the Michigan Growth Study were then converted to slow or normal growth status by slow being when the Z-score difference between the initial and final measurements is less than zero. The number of subjects with a slow versus normal growth status was compared to GHR polymorphism genotype. Statistical analysis of Hardy-Weinberg equilibrium and the changes in craniofacial length Z-scores in relation to a patient's genotype were performed using chi-square analysis.

Results: The genotype frequencies were in Hardy-Weinberg equilibrium. Z-score differences for the S-A measurement was the only one found to be significant (p=0.005).