M6A‑SNP: From genetics to epigenetics (Review)

Abstract

N⁶‑methyladenosine (m⁶A), the most abundant RNA modification, can participate in various physiological functions and pathological processes by regulating the expression or structure of genes due to its involvement in all aspects of RNA metabolism. Thus, the genetic variant that influences m⁶A, such as m6A‑associated single nucleotide polymorphism (m⁶A‑SNP), which is in close proximity to or in the methylation site, may be related to various pathological processes by increasing or decreasing the m⁶A methylation level due to the alteration of the nucleotide. The present review summarizes the recent advances made in m⁶A‑SNPs. Both the mining of genome‑wide association studies and the combined analysis of the m⁶Avar database with expression quantitative trait loci datasets have identified functional variants and causal genes associated with various diseases and have provided new direction for future studies on disease pathogenesis. In particular, some studies have indicated that base change in m⁶A‑SNPs lead to alterations in m6A modification levels, a conversion from genetics to epigenetics, and the expression variation of corresponding genes, which may affect the biological behavior of cells and explain the association of m⁶A‑SNPs with the risk or prognosis of diseases. In bladder cancer, colorectal cancer, coeliac disease, and pancreatic ductal adenocarcinoma, the overexpression of a specific allele alone can significantly modify the function of corresponding genes. On the whole, m⁶A‑SNPs play a pivotal role in all stages of diseases. In the future, the identification of m6A‑SNPs as disease biomarkers and ascertaining the functions of these m⁶A‑SNPs may prove beneficial. This would help to identify susceptible individuals in a timely manner and clarify the roles of corresponding genes in the occurrence and progression of diseases, and would also aid in the development of novel treatment strategies, ultimately improving patients' survival.