Comparison of cephalometric measurements between CL/P individuals with and without polymorphism in the BMP2 gene.

Objectives: The cleft lip palate (CL/P) is one of the most common birth defects frequently associated with genetic alterations. It has been shown that bone morphogenetic protein 2 (BMP2) plays an important role in palatogenesis in mice but there are no reports of BMP2 role in human clefts formation.

The aim of this study was to determine the presence of BMP2 single nucleotide polymorphisms (SNP) and compare the cephalometric measurements between CL/P individuals with and without SNP in this gene.
Methods: DNA was isolated from 46 CL/P and 50 healthy individuals and the three exons of the BMP2 gene were sequenced and analyzed. Twenty one cephalometric measurements obtained from lateral radiographs were compared in CL/P individuals bearing or not the novel BMP2 939 SNP. Statistic analysis were performed using Chi square and Student t test.

Results: We identified two nucleotide transitions in 929 and 939 position of BMP2 sequence. The 929 SNP was found in 47/50 healthy individuals and 37/46 CL/P individuals (p> 0.05). The 939 SNP was found in 10 out of 46 CL/P individuals and it was not present in healthy individuals (p<0,01) pointing out a significant relationship with CL/P phenotype. Individuals bearing the 939 SNP had significant differences in facial profile, maxillary position, mandibular size/position and growth pattern respect to the non-bearing SNP individuals (p<0,05).
Conclusions: Two SNPs were found in exon 2 of BMP2. The first one (located at position 929) had been previously reported but do not related with CL/P defect. The 939 SNP is a novel one and it was present in the 22% of CL/P individuals. This SNP was associated with phenotypic changes such as convex facial profile, maxillary and mandibular retrognathism, decrease in mandibular ascendant ramus height and greater vertical growth than non-bearing 939 SNP individuals.