rs2292832

This is a review of microRNA (miRNA) regulome dysregulation in atherosclerosis phenotypes. The paper summarizes studies on miRNA expression changes, DNA methylation in miRNA genes, and associations between single nucleotide polymorphisms (SNPs) in miRNA genes with atherosclerotic complications including coronary artery disease (CAD), myocardial infarction (MI), and ischemic stroke (IS). Key SNPs studied include rs2910164 (MIR146A) and rs3746444 (MIR499A/B), though results are often contradictory across different populations, with heterogeneous sample sizes ranging from 100-100K individuals.

This case-control study of 458 neonates (216 with sepsis, 242 controls) identified an association between rs41274221 polymorphism in the seed sequence of microRNA-25 and neonatal sepsis risk (OR=1.48, 95% CI=1.03-2.14, p=0.03). Functional studies confirmed that CD69 is a direct target of miR-25, with the polymorphism affecting the miR-25/CD69 regulatory axis, which influences IFN-γ production and immune response in neonates.

A case-control study of 878 colorectal cancer patients and 884 controls in a Han Chinese population found that SNP rs2682818 (C>A) in the miR-618 gene was associated with decreased CRC susceptibility. The AA and AC/AA genotypes showed protective effects with OR=0.54 (95% CI=0.37-0.79) and OR=0.82 (95% CI=0.68-0.99), respectively, compared to the CC genotype.

A case-control association study of 50 Saudi women with recurrent pregnancy loss (RPL) and 50 healthy controls examined six microRNA gene polymorphisms. Significant associations were found for miR-146a C>G (rs2910164, OR=2.29, 95% CI: 1.02-5.18, p=0.046) and miR-149 T>C (rs2292832, OR=2.67, 95% CI: 1.08-6.61, p=0.034) in heterozygous genotypes, with higher frequency in RPL patients compared to controls. Other polymorphisms (miR-10, miR-125, miR-323b, miR-499) showed no significant association with RPL.

Two miRNA genetic variants were identified as significantly associated with cardiometabolic phenotypes: rs11614913 in miR-196a2 associated with waist-to-hip ratio (P=1.7e-25), and rs174561 in miR-1908 associated with lipid and glucose traits. Functional analyses revealed these variants affect pre-miRNA processing and regulate target genes involved in fat distribution and lipid metabolism.

This comprehensive review analyzes microRNA-related single nucleotide polymorphisms (SNPs) in gastric cancer, focusing on the most commonly studied variants including pre-miR-146a rs2910164, pre-miR-196a2 rs11614913, pre-miR-149 rs2292832, and pre-miR-499 rs3746444. The paper reviews 45 studies examining associations between miRNA polymorphisms and gastric cancer risk, including 18 studies on rs2910164 showing conflicting results (OR range 0.81-1.58), 13 studies on rs11614913 with no overall significant association, and analysis of pri-miRNA, pre-miRNA, promoter, and 3'-UTR variants. Additional variants identified include rs712 in let-7 (OR = 3.05; 95% CI = 1.53-6.08), rs12904 in miR-200c (OR = 0.65; 95% CI = 0.50-0.85), and rs12537 in miR-181a (OR = 1.72; 95% CI = 1.36-2.16).

This case-control study of 353 Chinese colorectal cancer (CRC) patients and 540 healthy controls investigated associations between four pre-miRNA SNPs and CRC risk. rs11614913 T allele and CT/TT genotypes showed increased CRC risk (OR=1.99, 7.34, 13.66 respectively), while rs2910164 C allele was protective (OR=0.80). rs3746444 and rs2292832 showed no significant associations.

A two-stage association study in Chinese Han populations found that the TT genotype and T allele of rs11614913 in pre-miRNA-196a2 confer increased risk for Behcet's disease (combined OR=1.53, p=6×10⁻⁵), particularly in patients with arthritis manifestations (OR=1.89, p=5.3×10⁻³). Functional validation showed decreased miR-196a expression and increased Bach1 expression in TT carriers, leading to enhanced pro-inflammatory cytokine production (IL-1β and MCP-1). The variant did not associate with Vogt-Koyanagi-Harada syndrome or acute anterior uveitis in ankylosing spondylitis.

Meta-analysis of 11 case-control studies examining microRNA polymorphisms and oral squamous cell cancer (OSCC) risk. The microRNA-499 rs3746444 G allele showed strong association with increased OSCC risk (allele model OR=1.57, 95% CI=1.318-1.871, P<0.001; recessive model OR=3.165, 95% CI=1.777-5.637, P<0.00001). microRNA-146a rs2910164 showed weak protective effect in recessive model (CC genotype OR=0.874, 95% CI=0.768-0.994, P=0.041). No significant associations found for microRNA-196a2 rs11614913 or microRNA-149 rs2292832.

Hospital-based case-control study of 1,109 SCCHN cases and 1,130 controls examining genetic variants in four pre-miRNA genes. The hsa-mir-499 A>G variant (rs3746444) showed protective associations with reduced head and neck cancer risk (AG genotype OR=0.80, p=0.023). A combined risk genotype analysis showed increased risk with 4 risk genotypes (OR=1.40, p=0.040). Other pre-miRNA variants (hsa-mir-146a, hsa-mir-149, hsa-mir-196a2) showed no significant associations.

This PhD thesis presents a comprehensive study of microRNA (miRNA) SNPs and their association with breast cancer risk in Australian Caucasian populations. The study identified three key findings: rs2910164 in MIR146A showed significant association (p=0.03 and p=0.00013 in two populations); rs353291 in MIR145 showed significant differences in allele frequencies (p=0.041 and p=0.023); and rs4284505/rs7336610 in the MIR17HG cluster showed significant association with protective effect (OR=0.75, 95% CI: 0.60-0.94, p=0.012).