Association Between NOTCH3, JAG2Gene Polymorphisms With Non-syndromic Oral Clefts In A Chinese Population

Background:Nonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most common craniofacial development defects and birth defects. NOTCH signaling path-way takes a very important role in the development of regulation of cell growth, differentiation and apoptosis, NOTCH3and JAG2genes are the two members of the family. The study was the first time to investigate the association between the two genes polymorphisms with NSCLP in Chinese population from northwest China.Methods:A case-control association study in individuals with NSCLP (n=434) and healthy controls (n=457) was conducted. One SNP (rs12082) in NOTCH3gene and two SNPs(rs741859, rs2238286) in JAG2gene were genotyped by using PCR-RFLP followed by DNA sequencing.Results:The distributions of genotype and allele of three polymorphisms were significantly different in individuals with NSCLP compared to controls, with NOTCH3SNP rs12082A allele showing the association with susceptibility to NSCLP.,(P value=0.040, OR=1.322,95%CI=1.012～1.728); JAG2rs2238286AG genotype showing the most significant association with susceptibility to NSCLP.(Pvalue=0.005, OR=1.327,95%CI=1.089-1.617), while SNP rs741859TC genotype decreasing the risk for NSCLP.(Pvalue=0.001, OR=0.672,95%CI=0.526-0.859).Conclusions:It is the first report that the association of NOTCH3and JAG2genetic polymorphisms with NSCLP. In the present work, two SNP s of JAG2gene (rs2238286and rs741859) are significantly associated with NSCLP in a Chinese population. The results can provide some basic data for understanding pathogenesis of non-syndromic cleft lip and palate (NSCLP).