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

Oral Dis. 2018 Apr;24(3):422-428. doi: 10.1111/odi.12741. Epub 2017 Sep 18.

Abstract

Objective: MicroRNA (miRNA) processing genes play important roles in the craniofacial development. The aim of this 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 = .024, OR = 1.33, 95% CI = [1.04, 1.70]; GG + GA/AA: p = .037, OR = 1.29, 95% CI = [1.02, 1.63]), while rs493760 in DROSHA (CC/TT: p = .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.

Keywords: case-control study; genetic variant; microRNA; non-syndromic orofacial clefts.

MeSH terms

  • Argonaute Proteins / genetics
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cleft Lip / genetics*
  • Cleft Palate / genetics*
  • DEAD Box Protein 20 / genetics
  • DEAD-box RNA Helicases / genetics
  • Female
  • Haplotypes
  • Humans
  • Infant
  • Infant, Newborn
  • Karyopherins / genetics
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Minor Histocompatibility Antigens / genetics
  • Polymorphism, Single Nucleotide
  • RNA Processing, Post-Transcriptional / genetics*
  • RNA-Binding Proteins / genetics
  • Ribonuclease III / genetics*
  • Ribonucleoproteins, Small Nuclear / genetics

Substances

  • Argonaute Proteins
  • DGCR8 protein, human
  • GEMIN4 protein, human
  • Karyopherins
  • MicroRNAs
  • Minor Histocompatibility Antigens
  • PIWIL1 protein, human
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • XPO5 protein, human
  • DICER1 protein, human
  • DROSHA protein, human
  • Ribonuclease III
  • DEAD Box Protein 20
  • DEAD-box RNA Helicases