Genetic variants of microRNA processing genes and risk of non-syndromic orofacial clefts

Abstract

Objective

MicroRNAs (miRNAs) processing genes play important roles in the craniofacial development. The aim of the present study was to explore the associations between single nucleotide polymorphisms (SNPs) of miRNA processing genes with the risk of non-syndromic orofacial clefts (NSOC).

Methods

We genotyped 12 potentially functional SNPs from seven miRNA processing genes (GEMIN3, DROSHA, DGCR8, GEMIN4, PIWIL1, XPO5, and DICER) in a case-control study of 602 NSOC cases and 605 controls.

Results

Two SNPs were associated with the susceptibility of CL/P: rs10719 in DROSHA led to an increased risk of cleft lip with or without palate (CL/P) (GA/AA: P=0.024, OR=1.33, 95% CI=[1.04, 1.70]; GG+GA/AA: P=0.037, OR=1.29, 95% CI=[1.02, 1.63]), while rs493760 in DROSHA (CC/TT: P=0.049, OR=0.58, 95% CI=[0.34, 0.99]) could reduce the risk of CL/P. In addition, rs10719 (A)-rs493760 (C) haplotype contributed to a decreased risk of CL/P (OR=0.77, 95% CI=[0.63, 0.94]), whereas the rs10719 (G)-rs493760 (C) haplotype contributed to the increased risk of cleft palate only (CPO) (OR=2.70, 95% CI=[1.15, 6.35]). However, there was no difference observed in these SNPs after the Bonferroni correction.

Conclusion

Taken together, our results provided the potential evidence that rs10719 and rs493760 might contribute to the risk of CL/P, and suggested potential genetic basis and mechanisms of CL/P. The lack of association between these SNPs and CPO might be due to the limited sample size of CPO subgroup.

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