Introduction: The complex genetic diversity among human populations results from an assortment of factors acting at various sequential levels, including mutations, population migrations, genetic drift, and selection. Although there are a plethora of DNA sequence variations identified through genome-wide association studies (GWAS), the challenge remains to explain the mechanisms underlying interindividual phenotypic disparity accounting for disease susceptibility. Single nucleotide polymorphisms (SNPs) present in the sites for DNA methylation, transcription factor (TF) binding, or miRNA targets can alter the gene expression. The systematic review aimed to evaluate the complex crosstalk among SNPs, miRNAs, DNA methylation, and TFs for complex multifactorial disease risk. Methods: PubMed and Scopus databases were used from inception until May 15, 2019. Initially, screening of articles involved studies assessing the interaction of SNPs with TFs, DNA methylation, or miRNAs resulting in allele-specific gene expression in complex multifactorial diseases. We also included the studies which provided experimental validation of the interaction of SNPs with each of these factors. The results from various studies on multifactorial diseases were assessed. Results: A total of 11 articles for SNPs interacting with DNA methylation, 30 articles for SNPs interacting with TFs, and 11 articles for SNPs in miRNA binding sites were selected. The interactions of SNPs with epigenetic factors were found to be implicated in different types of cancers, autoimmune diseases, cardiovascular diseases, diabetes, and asthma. Conclusion: The systematic review provides evidence for the interplay between genetic and epigenetic risk factors through allele-specific gene expression in various complex multifactorial diseases.

中文翻译：

---

DNA 甲基化位点中的 SNP，转录因子结合，以及导致等位基因特异性基因表达和导致复杂疾病风险的 miRNA 靶点：系统评价

简介：人类种群中复杂的遗传多样性是由一系列作用于不同连续水平的因素造成的，包括突变、种群迁移、遗传漂变和选择。尽管通过全基因组关联研究 (GWAS) 发现了大量 DNA 序列变异，但仍需解释导致疾病易感性的个体间表型差异的潜在机制。DNA 甲基化位点、转录因子 (TF) 结合位点或 miRNA 靶点中存在的单核苷酸多态性 (SNP) 可以改变基因表达。该系统评价旨在评估 SNP、miRNA、DNA 甲基化和 TF 之间复杂的串扰，以应对复杂的多因素疾病风险。方法：从开始使用 PubMed 和 Scopus 数据库直到 5 月 15 日，2019. 最初，文章筛选涉及评估 SNP 与 TF、DNA 甲基化或 miRNA 相互作用的研究，这些相互作用导致复杂的多因素疾病中的等位基因特异性基因表达。我们还包括了为 SNP 与这些因素中的每一个的相互作用提供实验验证的研究。对多因素疾病的各种研究结果进行了评估。结果：共筛选出11篇SNPs与DNA甲基化相互作用的文章，30篇SNPs与TFs相互作用的文章，以及11篇miRNA结合位点SNPs的文章。发现 SNP 与表观遗传因素的相互作用与不同类型的癌症、自身免疫性疾病、心血管疾病、糖尿病和哮喘有关。结论：