Association of BRCA2 Gene Functional Polymorphisms with Nonsyndromic Cleft Lip With or Without Cleft Palate in a Chinese Population.

Abstract

Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a complex congenital disease affected by gene and environmental factors. Hereditary factors play an important role; however, its specific pathogenic genes and regulatory mechanisms remain unclear. In this study, we aimed to study the association between eight potentially functional single nucleotide polymorphisms (SNPs) of BRCA2 and MGMT genes and NSCL/P in a Chinese population through a case-control study. Materials and Methods: To investigate the relationship between potentially functional SNPs of the BRCA2 and MGMT genes and NSCL/P, we selected 200 affected patients and 200 unrelated normal controls in a Chinese population. The BRCA2 gene SNPs (rs11571836, rs144848, rs7334543, rs15869, rs766173, and rs206118) and MGMT gene SNPs (rs12917 and rs7896488) were genotyped by SNaPshot technique and then a preliminary bioinformatics analysis of the positive results was conducted. Results: Our study identified for the first time that BRCA2 was associated with NSCL/P in a Chinese population and rs11571836 G allele was protective against NSCL/P. Under four genetic models, rs11571836 had a significant correlation with NSCL/P. Preliminary bioinformatics analysis revealed that four potential matching sites (miR-1244, miR-1323, miR-562, and miR-633) were found for rs11571836 located in the 3' untranslated region of BRCA2. Conclusions: These results support the role of polymorphisms of BRCA2 in susceptibility to NSCL/P and its progression, but further research is necessary to elucidate the mechanism of the BRCA2 gene in the pathogenesis of NSCL/P.