Association between the FGFR1 rs13317 single nucleotide polymorphism and orbitale-nasion depth based on cephalometric images.

The fibroblast growth factor receptor 1 (FGFR1) gene plays an important role in craniofacial morphogenesis. In our previous study, an association between FGFR1 single nucleotide polymorphisms (SNPs) and craniofacial morphology was demonstrated in Japanese and Korean subjects. The present study aimed to evaluate the relationship between a common FGFR1 SNP (rs13317) with craniofacial morphology, increasing the number of measurements and examining Egyptian subjects (n = 191) in addition to the Japanese (n = 211) and Korean (n = 226) subjects. Genotyping for rs13317 was performed using the TaqMan assay, and its associations with 81 craniofacial measurements derived from lateral and posteroanterior cephalograms were analyzed by multiple regression analysis controlling sex and facial size. The results from each of the populations were then statistically combined. In the Egyptian subjects, rs13317 was significantly associated with the nasion-orbitale depth (P = 0.00040), and a suggestive association was also observed in the Japanese (P = 0.037) and Korean subjects (P = 0.045). The combined analysis revealed that only the nasion-orbitale depth showed a significant association (P = 0.000062) and that several measurements showed a suggestive association. Our results strongly indicate that rs13317 is associated with a smaller depth between the nasion and orbitale, representing a relative protrusion of the cheekbones and retrusion of the nasal root. A similar characteristic is also observed in individuals with Pfeiffer syndrome, which is caused by a dysfunctional FGFR1 mutation.