Potential interactions among single nucleotide polymorphisms in bone‐ and cartilage‐related genes in skeletal malocclusions

Abstract

Objective To investigate SNPs in bone‐ and cartilage‐related genes and their interaction in the aetiology of sagittal and vertical skeletal malocclusions. Settings and sample population This study included 143 patients and classified as follows: skeletal class I (n = 77), class II (n = 47) and class III (n = 19); maxillary retrusion (n = 39), protrusion (n = 52) and well‐positioned maxilla (n = 52); mandibular retrognathism (n = 50), prognathism (n = 50) and well‐positioned mandible (n = 43); normofacial (n = 72), dolichofacial (n = 55) and brachyfacial (n = 16). Materials and methods Steiner's ANB, SNA, SNB angles and Ricketts’ NBa‐PtGn angle were measured to determine the skeletal malocclusion and the vertical pattern. Nine SNPs in BMP2, BMP4, SMAD6, RUNX2, WNT3A and WNT11 were genotyped. Chi‐squared test was used to compare genotypes among the groups. Multifactor dimensionality reduction (MDR) and binary logistic regression analysis, both using gender and age as co‐variables, were also used. We performed Bonferroni correction for multiple testing. Results Significant associations at P < .05 were observed for SNPs rs1005464 (P = .042) and rs235768 (P = .021) in BMP2 with mandibular retrognathism and for rs59983488 (RUNX2) with maxillary protrusion (P = .04) as well as for rs708111 (WNT3A) with skeletal class III (P = .02; dominant model), rs1533767 (WNT11) with a brachyfacial skeletal pattern (P = .01, OR = 0.10; dominant model) and for rs3934908 (SMAD6) with prognathism (P = .02; recessive model). After the Bonferroni correction, none of the SNPs remained associated. The MDR predicted some interaction for skeletal class II, dolichofacial and brachyfacial phenotypes. Conclusion Our results suggest that SNPs in BMP2, BMP4, SMAD6, RUNX2, WNT3A and WNT11 could be involved in the aetiology of sagittal and vertical malocclusions.

Parathyroid Hormone Gene and Genes Involved in the Maintenance of Vitamin D Levels Association with Mandibular Retrognathism

“…The prevalence of skeletal malocclusion ranges in different ethnic groups [ 34 ]. In the orthodontic population studied here with evaluated Brazilian patients, skeletal class II malocclusion affects about 30% of the sample [ 11 , 37 ] and mandibular retrognathism affects 35% of the sample [ 8 ]. Retrognathism is a much more frequent condition than mandibular prognathism; however, its etiology has been the subject of only a few studies.…”

“…Most studies on the genetic background of skeletal malocclusion have focused on prognathism and Class III malocclusion, which is less frequent in the general population. Studies on genes involved in skeletal Class II malocclusion, retrognathism, and micrognathia are rarer [ 2 ] and only a few genes and SNPs have been evaluated thus far [ 7 , 9 , 10 , 11 , 38 , 39 ]. Therefore, the present study aimed to explore the role of some SNPs as well as their interaction in the mandibular retrognathism phenotype in humans.…”

“…Multifactor dimensionality reduction (MDR) [ 31 ] was done to identify SNP-SNP interactions using gender and age as co-variables as previously reported [ 11 ]. Two specific software programs (Multifactor Dimensionality Reduction 3.0.2 [ 31 ], and MDR Permutation Testing Module 1.0 beta 2 [ 32 ], available in sourceforge.net/projects/mdr/files (accessed on 2 April 2021)), were used to perform a 10-fold cross-validation consistency (CVC), testing balancing accuracy (TBA), and the 1000 permutation test to determine the statistical significance of the models.…”

“…This is the most common type of genetic variation in humans, and it has been stated that these variants could explain differences in individual predisposition to present complex traits [ 8 ]. Previous studies have shown that MR was associated with SNPs in various genes such as Myosin 1H ( MYO1H ) [ 9 ], Matrilin 1 ( MATN1 ) [ 7 ], ADAM Metallopeptidase with Thrombospondin Type 1 Motif 9 ( ADAMTS9 ) [ 10 ], and Bone Morphogenic Protein 2 ( BMP2 ) [ 11 ] genes. In addition, SNPs in the gene encoding growth hormone receptor (GHR) have been associated with variations in the mandibular pattern including prognathism [ 5 , 12 ], supporting that genes coding for hormones, hormone receptors, hormone precursors, and molecules involved in hormonal synthesis could also be involved in the etiology of other phenotypes.…”

Genetic variants in bone morphogenetic proteins signaling pathway might be involved in palatal rugae phenotype in humans

“…Both genetic variants associated with fragmentary and secondary palatal rugae were previously associated with other oral phenotypes. The genetic variant rs1005464 in BMP2 has been associated with a variety of conditions including dental crowding 22 and mandibular retrognathism 23 . BMP4 is a widely studied gene as an etiologic factor involved in oral cleft establishment, which is a congenital alteration in palate formation.…”