Association Of Novel Human Genes ZNF347 And ZNF426 Variants With Non-syndromic Cleft Lip With Or Without Cleft Palate In Chinese Population

Background:Cleft lip and or palate (CLP) is the most frequent human craniofacial birth malformations which represents a class of nonlethal congenial defect of complex etiology and genetic heterogeneity. And approximately 70% of CLP occurs is isolated symptoms without other apparent or cognizable structural deformities, which is called non-syndromic cleft lip and or palate (NSCL/P). As a complex polygenic inherited disorder, NSCL/P is affected synthetically by genetic and environmental factors. Zinc finger proteins play an important role in the embryonic development and maybe associated with NSCL/P. The present work aimed to evaluate the association between ZNF347 gene, ZNF426 gene polymorphisms and NSCLP in Chinese population.Methods:Three tagSNPs named rs10417172, rs2195310 and rs2042199, which represent the overall variabilities of ZNF347 gene and ZNF426 gene, were discovered by Exome Sequencing. 502 patients with NSCL/P and 482 normal controls were genotyped by PCR-RFLP. All statistical analyses were performed with SPSS 19.0. A value of p< 0.05 was regarded as significant, and haplotype was constructed by SHEsis software 17.0. Multiple testing was corrected by Bonferroni and false discovery rate (FDR) methods.Results:The frequencies of rs10417172 CT and rs2195310 AG were significantly lower in NSCLP cases group (13.1%,15%) than that in controls group (20%,23%) with p-value=0.004, 0.005, corrected p value (p-corr)<0.05 and with odds ratio (OR)=1.657,95% confidence interval [CI]:1.177-2.333, OR=1.582,95% CI:1.145-2.186. The minor allele C of rs10417172 and also appeared to be susceptible to NSCLP with p-value=0.002, p-corr<0.05, OR=1.648,95% CI: 1.202-2.260.After stratification in the all samples, the frequency of rs10417172 CT and rs2195310 AG showed stronger association in male patients and cleft palate only patients.Conclusions:This is the first report that two SNPs of ZNF347 (rs10417172 and rs2195310) are significantly associated with NSCL/P in Chinese population. These findings provide evidence that genetic variations of the ZNF347 may be associated with NSCL/P risk in Chinese population.