Association of Growth Hormone Receptor Gene Variants with Mandibular Form in an Egyptian Population

A significant genetic component is involved in the development of the craniofacial form. Recently, the growth hormone receptor gene (GHR) variants rs6180 and rs6184 were associated with variations in mandibular form. To confirm these findings we evaluated the relationship between these GHR variants and mandibular form in a cohort of Egyptian individuals with a normal skull form. The patients consisted of 191 unrelated Egyptian adults (92 males, 99 females; 18-55 years). Allele frequencies of the rs6180 and rs6184 variants were determined from genomic DNA extracted from saliva using the Taqman genotyping assay. Lateral and posteroanterior cephalometric tracings were used to obtain 19 mandibular measurements. The association between the GHR variants and the mandibular measurements was examined using regression analysis. The frequency of the minor rs6184 variant was very low at 1.5%: therefore, association studies were not performed for this variant. The rs6180 variant was not associated with any of the measurements representing mandibular form in our study cohort. The frequency of the rs6184 variant was very low in our cohort of Egyptian subjects. We also found no association between the rs6180 variant and the measurements representing the mandibular form. By excluding the involvement of these GHR variants in influencing mandibular form, our results may help to identify the actual variant(s) affecting the mandibular form in the Egyptian population

Contribution of <i>FGFR1</i> Variants to Craniofacial Variations in East Asians

<div><p><i>FGFR1</i> plays an important role in the development of the nervous system as well as the regulation of the skeletal development and bone homeostasis. Mutations in <i>FGFR1</i> genes affect skull development, specifically suture and synchondrosis, resulting in craniosynostosis and facial abnormalities. We examined subjects with normal skull morphology for genetic polymorphisms that might be associated with normal craniofacial variations. Genomic DNA was obtained from 216 Japanese and 227 Korean subjects. Four <i>FGFR1</i> SNPs, namely, rs881301, rs6996321, rs4647905, and rs13317, were genotyped. These SNPs were tested for association with craniofacial measurements obtained from lateral and posteroanterior cephalometries, in which principle component analysis was performed to compress the data of the craniofacial measurements. We observed that SNPs rs13317 and rs6996321 were correlated with the overall head size and midfacial development, indicating that <i>FGFR1</i> SNPs played crucial roles in the normal variation of human craniofacial morphology. Subjects with the derived alleles of SNPs rs13317 and rs6996321 had a small face and a facial pattern associated with a retruded midface and relatively wide-set eyes. These facial features were similar to but were milder than those of individuals with Pfeiffer syndrome, which is caused by a dysfunctional mutation in <i>FGFR1</i>.</p></div

Lateral and posteroanterior cephalometric tracing showing the landmarks used to obtain craniofacial measurements.

<p>(V) Vertex, (Eu) eunion, (Lo) latero-orbitale, (Or) orbitale, (Zy) zygion, (Cd) condylion, (Ko) Koronoid, (Ma) mastoid, (NC) nasal cavity, (Cr) crista galli, (ANS) anterior nasal spine, (Go) gonion, (Ag) antegonion, (Me) menton, (G) glabella, (N) nasion, (S) sella turcica, (SOr) supra orbitale, (R) rhinion, (KR) key ridge, (Pr) prosthion, (A) point A, (PNS) posterior nasal spine, (Id) infradentale, (Gn) gnathion. The NA plane was used as a reference to measure the anteroposterior position of G, SOr, R, Or, and KR, with positive and negative values indicating whether the landmark is in an anterior and posterior direction, respectively, from the NA plane.</p

Allele frequencies and LD coefficients of <i>FGFR1</i> SNPs.

<p>Allele frequencies and LD coefficients of <i>FGFR1</i> SNPs.</p

PC loading for each PC. (A) PCA of cranial measurements. (B) PCA of mandibular measurements.

<p>PC loading for each PC. (A) PCA of cranial measurements. (B) PCA of mandibular measurements.</p

Regression analysis to determine the association of FGFR1 SNPs with craniofacial morphological variation in Japanese and Korean subjects.

<p>Regression analysis to determine the association of FGFR1 SNPs with craniofacial morphological variation in Japanese and Korean subjects.</p