Genetic variants of MGMT, RHPN2, and FAM49A contributed to susceptibility of nonsyndromic orofacial clefts in a Chinese population.

BACKGROUND: The role of underlying genetic factors in the pathogenesis of nonsyndromic orofacial clefts (NSOC) remains poorly understood. Although genomewide association studies (GWASs) of NSOC have successfully identified a large number of novel genetic risk loci, association results of replication studies are inconsistent across different populations.

METHODS: Six single nucleotide polymorphisms (SNPs) (rs7922405 at 10q26.3, rs73039426 at 19q13.11, rs7552 at 2p24.2, rs1788160 at 8q22.2, rs9381107 at 6p24.3, and rs17095681 at 10q25.3) were analyzed for an association with NSOC in 1062 participants of Chinese descent (596 patients and 466 controls). We applied the multifactor dimensionality reduction (MDR) method to detect potential gene-gene (G × G) interactions in the six SNPs.

RESULTS: The genotype or allele frequencies of SNPs rs7922405, rs73039426, and rs7552 showed significant differences between the controls and patients with NSOC, whereas no association was shown between three SNPs (rs1788160, rs17095681, and rs9381107) and NSOC. MDR analysis did not reveal significant G × G interactions for susceptibility to NSOC.

CONCLUSION: We confirmed that three genes (rs7922405 of MGMT, rs73039426 of RHPN2, and rs7552 of FAM49A) may contribute to NSOC in Chinese populations. MGMT and RHPN2 are associated with NSOC, which is herein demonstrated for the first time.