Family-based study of association between ENPP1 genetic variants and craniofacial morphology.
BACKGROUND
Human craniofacial morphology is characterized by considerable diversity among individuals. The ENPP1 gene is essential for bone physiology. However, the potential effects of its genetic variants on head size phenotypes have not yet been studied.


OBJECTIVE
The aim of this research was to investigate the association of polymorphisms in the ENPP1 locus with normal variability of craniofacial phenotypes.


METHODS
Fourteen SNPs and 13 haplotypes in the ENPP1 locus were tested for association with six head size traits in 1042 Western Eurasian individuals.


RESULTS
The most significant and consistent association was observed between upper facial height and the polymorphisms located near the promoter region and upstream from ENPP1 gene (p = 0.00009), which remained significant after adjustment for multiple testing. Additionally, association signals were detected between head breadths and lower face height, and markers residing in or close to the promoter and 3' untranslated regions of the ENPP1 gene (p < 0.05).


CONCLUSIONS
The findings obtained in this study suggest that the upstream, promoter and 3' untranslated regions in the ENPP1 locus harbor genetic variants affecting different aspects of craniofacial morphology. Further research is required to validate the relevancy of the potentially functional ENPP1 regions to normal and pathologic craniofacial growth.
Ermakov
Sergey
S
Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Rosenbaum
Michael G
MG
Malkin
Ida
I
Livshits
Gregory
G
D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005145:Face / Q000033:anatomy & histology*; D005190:Family; D005260:Female; D005546:Forehead / Q000033:anatomy & histology; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006257:Head / Q000033:anatomy & histology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009666:Nose / Q000033:anatomy & histology; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011755:Pyrophosphatases / Q000235:genetics*; D012426:Russia; D012886:Skull / Q000033:anatomy & histology; D055815:Young Adult
D020413:3' Untranslated Regions; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases