Identification of SNP Markers on 1p36 and Association Analysis of EPB41 with Mandibular Prognathism in a Chinese Population

Objective: The results of a genome-wide scan suggested that chromosome locus 1p36 might be linked to the etiology of mandibular prognathism (MP) amongst Asian ethnicities. In this study, we performed a two-stage case-control association study to determine whether one or more genes that confer susceptibility to MP are located within this genomic region.

Design: In the first stage of the study, we examined 103 single nucleotide polymorphisms (SNPs) on 1p36 across an 8.6Mb critical region and within four candidate genes in 158 cases and 147 controls to identify genes associated with MP. In the second stage of the study, we examined an additional 23 SNPs within the erythrocyte membrane protein band 4.1 (EPB41) gene in 211 cases and 224 controls.

Results: Four SNPs located in the EPB41 gene showed possible allelic and genotypic associations with MP (P<0.03 and P<0.05, respectively) in the first stage. In the analysis of single SNPs in the second stage, the allele of rs4654388 showed the strongest significant association with MP (P=0.008) and the rs4654388 G-allele was associated with a significantly increased risk of MP (OR: 1.78, 95% CI: 1.16-2.74). Haplotype analysis revealed that MP was associated significantly with haplotype GTTCAGGT (P(corrected)=0.031), which included the rs4654388 G-allele.

Conclusions: An association between genetic polymorphisms in the EPB41 gene and MP has been observed. Although the polymorphisms which may contribute to MP have not been determined, the results of our study suggest that the EPB41 gene could confer susceptibility to MP.