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

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.