Evidence for a Role of GHR Gene with Mandibular Morphology in the East Asian Population, and Allelic Heterogeneity in Different Ethnicities

  • Prof Tetsutaro Yamaguchi, Department of Orthodontics, School of Dentistry, Showa University, Japan
  • Dr Yoko Tomoyasu, Department of Orthodontics, School of Dentistry, Showa University, Japan
  • Dr Eun Kang, Korea
  • Professor Atsushi Tajima, Division of Molecular Life Science, Division of Genetic Information, School of Medicine, Tokai University, Japan
  • Dr Miyuki Watanabe, Department of Orthodontics, School of Dentistry, Showa University, Japan
  • Professor Soo Park, Korea
  • Prof Ituro Inoue, Department of Molecular Life Science, School of Medicine, Tokai University, Japan
  • Prof Koutaro Maki, Department of Orthodontics, School of Dentistry, Showa University, Japan

Objective: Growth hormone plays a major role in the growth and development of the craniofacial complex by directly and indirectly. Growth hormone receptors (GHRs) have been identified in the mandibular condyle as a site-specific manner. Mutations of the gene have been associated with Laron syndrome, showed significant decreases in measures of vertical facial growth. This study examined the association between six polymorphisms in exon 3 and 10 of GHR and craniofacial morphology in the East Asian population, and further characterized the importance of GHR gene by examining the allelic frequencies of these polymorphisms in a multi-ethnic population.
Methods: We studied the relationship between six polymorphism genotypes and craniofacial linear measurements obtained from lateral cephalograms of 326 East Asian subjects (167 Japanese, 159 Korean). The allelic frequencies in a multi-ethnic population (Han Chinese, African American, European American, and Hispanic) were also observed. The protocol used in this study was approved by the relevant Ethical Committee.
Results: There was a significant association between P561T and C422F polymorphisms and mandibular ramus height (P = 0.01). The polymorphisms was significantly correlated with the level of expression (P = 0.02) from the database of the Gene Expression Variation project. These polymorphisms were found almost exclusively in the Asian population, with extremely small frequencies in other populations.
Conclusions: GHR polymorphisms are associated with mandibular ramus height in the East Asian population, but this association is likely to be different in other ethnic groups, and may partly explain the differing craniofacial morphology seen among different ethnicities.