RESUMO
INTRODUCTION: The purpose of this study was to extend an association study from chromosome 1 to the whole genome (genome-wide association study) to find susceptibility loci of mandibular prognathism. METHODS: Two hundred forty patients diagnosed with mandibular prognathism and 360 healthy controls of Japanese descent were recruited. The typing of microsatellites covering the whole genome was conducted using a pooled DNA method. Upon completion of the first and second screenings with pooled DNA, the positive microsatellite markers from both the first and second typings were retyped using individual-subject DNA samples to confirm the significance of allele frequency. RESULTS: Six microsatellites (D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, and D15S0154i) showed differences between allele frequencies of the subjects and controls at P <0.001. D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, and D15S0154i were located on chromosomes 1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22, respectively. SSX2IP, PLXNA2, RASA2, TCF21, CALN1, and RORA were suggested as candidate genes. CONCLUSIONS: The genome-wide association study using microsatellites suggested that 6 loci (1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22) were susceptibility regions of mandibular prognathism. The locus 1p22.3 was supported by a previous linkage analysis, and the other 5 were novel loci.
Assuntos
Má Oclusão Classe III de Angle/genética , Repetições de Microssatélites/genética , Estudos de Casos e Controles , DNA/genética , Frequência do Gene/genética , Ligação Genética/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , HumanosRESUMO
INTRODUCTION: Attempts have been made to identify susceptibility genes of mandibular prognathism by genome-wide linkage studies, but the results of susceptibility loci are inconsistent. There has been no genome-wide association study of mandibular prognathism. Our objective was to perform a genome-wide association study using 23,465 microsatellite markers to detect mandibular prognathism susceptibility regions. METHODS: The study was based on the pooled DNA method, including 2 steps of screening on the whole genome and subsequent individual genotyping, with 240 experimental subjects and 360 control subjects from the Japanese population. RESULTS: Two suggestive associations on chromosomes 1q32.2 (D1S1358i: P = 4.22 × 10(-4)) and 1p22.3 (D1S0411i: P = 6.66 × 10(-4)) were shown, and PLXNA2 and SSX2IP were suggested to be candidate genes; 1p22.3 flanked the region indicated by previous linkage analysis. CONCLUSIONS: The results of the genome-wide association study showed that 2 loci (1q32.2 and 1p22.3) are likely to be susceptibility regions of mandibular prognathism: 1p32.2 is a novel locus, and identification of 1p22.3 supports the results of previous linkage analysis.
