Genetic polymorphisms underlying the skeletal Class III phenotype

Introduction: Our goal was to verify the association between candidate polymorphisms and skeletal Class III malocclusion in a well-characterized homogeneous sample set. Methods: Thirty-five single-nucleotide polymorphisms were studied from 10 candidate loci in 54 Class III subjects and 120 controls. Skeletal Class III characteristics included ANB angle less than 0 degrees, SNB angle greater than 83 degrees (mandibular prognathism), SNA angle less than 79 degrees (maxillary deficiency), Class III molar relationship, and negative overjet. Inclusion criteria for the controls were ANB angle between 0 degrees and 4 degrees, Class I molar relationship, and normal overjet. Chi-square and Fisher exact tests and principal component (PC) analysis were used to determine overrepresentation of marker alleles with alpha of 0.05. Odds ratios and 95% confidence intervals were calculated. Results: MYO1H (rs10850110 A < G) (P < 0.01; odds ratio, 7.44 [4.02-13.77]) was associated with an increased risk for the mandibular prognathism phenotype. These results were confirmed by PC analysis, which showed 4 PCs representing the sample variations (PC1, 37.24%; PC2, 20.02%; PC3, 12.18%; and PC4, 11.40%), and PC1 was associated with MYO1H (P < 0.001). We also found by PC analysis associations between MYO1H (P < 0.001) and GHR (rs2973015 A > G) (P = 0.001) with PC2 and between FGF10 (rs593307 A > G) (P 5 0.001) with PC4. Conclusions: Polymorphism in MYO1H could be used as a marker for genetic susceptibility to Class III malocclusion with mandibular prognathism, and polymorphisms in GHR and FGF were associated with maxillomandibular discrepancies. This study may contribute to improved diagnosis and further research assessing possible differences in treatment responses based on genetic polymorphisms.