Objective: Leptin receptor gene (LEPR) is involved in bone growth. The association of two single nucleotide polymorphisms (SNPs) rs10449758 and rs7418057 in LEPR and mandibular retrognathism has been found from our previous study. This project was carried out to further investigate the polymorphisms of LEPR in mandibular retrognathism subjects and to validate the association in southern Chinese population.
Methods: 162 mandibular retrognathism subjects and 198 subjects with normal sagittal jaw relationship were recruited into this case-control study. Peripheral veinous blood was extracted to harvest genomic DNA. 32 SNPs, which flank the region of SNPs rs10449758 and rs7418057 with a medium to high r2 value of 0.5-0.9, were selected for further test. Genotyping was performed with the Sequenom platform. Association test,Hardy-Weinberg equilibrium test and Linkage Disequilibrium test were executed.
Results: 13 SNPs were found to have nominal genotypic significant p values. Among the 13 SNPs, 7 showed nominal allelic significant p values as well. Furthermore, a 9kb LD block which harbored 12 significant polymorphisms showed different haplotype structure distribution between two groups. Haplotype (GGCCTGTTCATCT) was more frequently identified in case group (0.864 versus 0.791), while haplotype (TATTCACATAGTC) was more prevalent in controls (0.056 versus 0.124).
Conclusions: We detected the association between polymorphisms in LEPR and mandibular retrognathism. This confirms the previous documented association, and help to explain the etiology of this trait. Following validation in bigger samples and function analysis of LEPR in maxillofacial skeletal morphology could be incorporated to clearly elaborate the genetic control in craniofacial morphological development.