Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Oral Dis. 2018 Apr;24(3):422-428. doi: 10.1111/odi.12741. Epub 2017 Sep 18.
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).
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.
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.
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.
微小 RNA（miRNA）加工基因在颅面发育中发挥重要作用。本研究旨在探讨 miRNA 加工基因单核苷酸多态性（SNP）与非综合征性口面裂（NSOC）风险的关系。
我们在 602 例 NSOC 病例和 605 例对照的病例对照研究中，对 7 个 miRNA 加工基因（GEMIN3、DROSHA、DGCR8、GEMIN4、PIWIL1、XPO5 和 DICER）中的 12 个潜在功能 SNP 进行了基因分型。
有 2 个 SNP 与 CL/P 的易感性相关：DROSHA 中的 rs10719 导致唇裂伴或不伴腭裂（CL/P）的风险增加（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]），而 DROSHA 中的 rs493760（CC/TT：p=0.049，OR=0.58，95%CI=[0.34，0.99]）可降低 CL/P 的风险。此外，rs10719（A）-rs493760（C）单倍型可降低 CL/P 的风险（OR=0.77，95%CI=[0.63，0.94]），而 rs10719（G）-rs493760（C）单倍型仅可增加腭裂的风险（CPO）（OR=2.70，95%CI=[1.15，6.35]）。然而，在进行 Bonferroni 校正后，这些 SNP 之间没有差异。
总之，我们的结果提供了潜在的证据，表明 rs10719 和 rs493760 可能导致 CL/P 的风险，并提示了 CL/P 的潜在遗传基础和机制。这些 SNP 与 CPO 之间没有关联可能是由于 CPO 亚组的样本量有限。
