Associations between common genetic variants in microRNAs and Hirschsprung disease susceptibility in Southern Chinese children

Abstract

Introduction: Hirschsprung disease (HSCR), characterized by the defective migration of enteric neural crest cells, is a severe congenital tract disease in infants. Its etiology is not clear at present, although a genetic component plays an important role in its etiology. Many studies focused on the polymorphisms of microRNA (miRNA) in several disease progressions have been reported, including HSCR. However, the findings remain inconclusive. The present study aimed to explore the association of genetic variants in miRNAs and HSCR susceptibility in Southern Chinese children. Methods: Five single nucleotide polymorphisms (SNPs) (miR-146A rs2910164, miR-4318 rs8096901, miR-3142 rs2431697, miR-3142 rs2431097 and miR-3142 rs5705329) were included to be genotyped in the stratified analysis through the Mass ARRAY iPLEX Gold system (Sequenom, San Diego, CA, USA) conducted on all the samples, comprising 1470 cases and 1473 controls. After quality control, the minor allele frequency was compared in cases and controls to analyze the association between SNPs and HSCR using PLINK 1.9 (https://www.cog-genomics.org/plink) and multiple heritability models were tested (additive, recessive and dominant models). Results: Our results indicated that miR-4318 rs8096901 polymorphisms were associated with HSCR susceptibility in Southern Chinese children, especially in shortsegment HSCR (S-HSCR) patients after stratified analysis. Conclusions: In summary, we report that miR-4318 rs8096901 was associated with HSCR, especially in SHSCR patients.

Pathogenic roles of microRNAs and competing endogenous RNAs in Hirschsprung disease (HSCR): Potential diagnostic markers for HSCR

“…The findings demonstrated that the genetic variation of miR-938rs2505901 influenced HSCR susceptibility and was connected to miR-938 expression. Wu et al 21 conducted a stratified analysis of 1470 cases and 1473 controls and found that miR-4318 rs8096901 polymorphism was associated with HSCR susceptibility in children in southern China, particularly in patients with shortsegment HSCR (S-HSCR). Changes in HSCR susceptibility were linked to three positive 3 0 UTR variations in mitogen-activated protein kinase10 (MAPK10).…”

INTS-MFS: A novel method to predict microRNA-disease associations by integrating network topology similarity and microRNA function similarity

“…MicroRNAs (miRNAs) are approximately 22-nucleotide noncoding RNAs, act as an important regulator involved in posttranscriptional regulation of gene expression (Bartel, 2004). Recently, increasing evidence has showed that the development and progression of various complex human diseases result from the mutation and functional disorders (Alvarez-Garcia and Miska, 2005;Lynam-Lennon et al, 2009;Wu et al, 2021). Furthermore, more and more studies have indicated that miRNAs could influence multiple stages of the biological processes (Chen et al, 2018a;Lee et al, 1993), such as differentiation (Karp and Ambros, 2005), cell development (Miska, 2005), and viral infection (Miska, 2005).…”

Predicting miRNA-disease association through combining miRNA function and network topological similarities based on MINE

“…The identification of associations between diseases and miRNAs has attracted much attention. Accumulating evidence has indicated that miRNAs play key roles in biological processes and complex diseases ( Alvarez-Garcia and Miska, 2005 ; Lynam-Lennon et al., 2009 ; Wu et al., 2021 ). Therefore, predicting disease-associated miRNAs will be beneficial for researching the mechanisms of pathogenicity and promoting the diagnosis and treatment of human diseases.…”