rs11614913

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.

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 is a perspective and mission statement from the GEMSTONE Consortium reviewing current and future approaches for functional validation of skeletal genetic disease using cellular, molecular, and animal-modeling techniques. The paper discusses how large GWAS have identified 518 loci associated with bone mineral density (BMD), and reviews strategies for bridging the gap between genetic association and causality through functional investigation, including the role of miRNAs (e.g., rs11614913 in MIR196A2 and rs1048201 in FGF2 3'UTR associated with lumbar spine BMD), endophenotypes, Mendelian randomization, and animal models in understanding skeletal diseases like osteoporosis.

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.

This PhD thesis investigated pharmacogenetics of microRNAs and immune system genes in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy. In 265 LARC patients, five SNPs were identified as predictive biomarkers of pathological response: DROSHA-rs10719 (OR=1.87, p=0.0274) and SMAD3-rs17228212 (OR=2.01, p=0.0049) were unfavorable, while SMAD3-rs744910 (OR=0.45, p=0.0153), SMAD3-rs745103 (OR=0.48, p=0.0471), and TRBP-rs6088619 (OR=0.39, p=0.0125) were protective. In 235 LARC patients, three prognostic biomarkers for 2-year disease-free survival were identified: IL17F-rs641701 (HR=3.23, p=0.003), IL17F-rs9463772 (HR=2.89, p=0.002), and STAT3-rs8069645 (HR=0.50, p=0.044).

This study found that the rs11614913 polymorphism in miR-196a-2 is associated with vitiligo risk, particularly in combination with elevated serum tyrosinase (Tyr) levels. The C allele enhanced the miRNA's inhibitory effect on Tyr expression through suppression of its target gene Tyrp1, reducing intracellular ROS levels and apoptosis in melanocytes. Individuals with TT/TC genotypes and higher Tyr levels (≥80.69 ng/L) had significantly increased vitiligo risk (adjusted OR 4.15; 95% CI 1.49-11.58) compared to CC genotype with lower Tyr levels.

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.

Case-control study in Chinese Han population of 381 ESCC cases and 426 controls examining microRNA-related SNPs. Variant rs11614913 (TT genotype) in miR-196a-2 was associated with reduced ESCC risk (OR=0.62, 95% CI: 0.39-0.99), as was rs1595066 (AA genotype) in ErbB4 (OR=0.38, 95% CI: 0.24-0.61). Haplotype analysis identified protective and risk haplotypes in ErbB4 involving rs1595066 and rs16845990. Gene-environment interaction analysis identified family history and smoking as important ESCC risk factors.

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.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

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 examined the association between miR-146a rs2910164 polymorphism and colorectal cancer (CRC) susceptibility in a Chinese population of 1,147 cases and 1,203 controls. The study found that the GC/CC genotypes were significantly associated with reduced CRC risk (adjusted OR = 0.78, 95% CI = 0.66-0.93) compared to GG homozygotes. The protective effect was more pronounced in non-smokers, non-drinkers, older subjects, and those without family history of cancer. A meta-analysis of 29 studies (15,398 cases and 18,564 controls) found no significant overall association in the allelic model but showed ethnicity-specific effects.

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.

This case-control association study examined 442 Chinese advanced non-small cell lung cancer patients receiving platinum-based chemotherapy and found that rs11614913 in hsa-miR-196a2 was significantly associated with severe overall toxicity. The homozygous CC genotype showed increased risk of grade 3-4 toxicity (OR=1.73, p=0.02), with stronger effects in patients treated with cisplatin (OR=2.04, p=0.008) or gemcitabine plus platinum (OR=4.46, p=0.006), and in male or younger patients.

A case-control study of 916 Chinese CAD patients and 584 controls found that hsa-mir-499 rs3746444 GG variant increased CAD risk 3.23-fold (OR=3.23, 95% CI=1.56-6.67). hsa-mir-196a2 rs11614913 CC/CT variants were not associated with increased CAD risk but were associated with 34-35% increased risk of poor prognosis (HR=1.34-1.35). These miRNA SNPs may contribute to CAD susceptibility and prognosis in Chinese populations.

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.

A case-control study of 136 oral premalignant lesion (OPL) patients and 136 matched controls examined 31 SNPs in microRNA biogenesis pathway genes. The variant allele of rs7372209 in mir26a-1 increased OPL risk (OR 2.09, 95% CI 1.23-3.56), as did rs3742330 in DICER (OR 2.09, 95% CI 1.03-4.24), while rs197412 in GEMIN3 reduced risk (OR 0.58, 95% CI 0.33-0.99). A combined analysis of five SNPs with borderline significant associations showed a dramatic cumulative effect on OPL risk (P for trend <0.0001), with the high-risk group having 21-fold increased odds.

A hospital-based case-control study in Chinese population (643 glioma cases, 656 controls) examined the miR-196a T/C polymorphism (rs11614913) and glioma risk. The CC genotype was associated with decreased glioma risk (OR = 0.74, 95% CI: 0.56-0.98), with stronger associations in adult glioma (OR = 0.73), male glioma (OR = 0.69), and glioblastoma (OR = 0.58). This was the first study to investigate this miRNA variant's association with glioma, contrasting with previous findings in lung and breast cancer.

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).

This study evaluated 40 SNPs in microRNA-related genes for associations with colorectal cancer prognosis in 426 Korean patients. In univariate analysis, mir492 C>G (rs2289030) was significantly associated with progression-free survival (PFS 70.8% for C/C vs 62.6% for C/G vs 60.3% for G/G, P=0.0426), but no associations remained significant in multivariate analysis. The authors concluded that none of the 40 miRNA-related gene polymorphisms tested were independent prognostic markers for surgically resected colorectal cancer.

A case-control study in an Iranian population (100 cases, 100 controls) found that the rs2682818 polymorphism in miR-618 is associated with increased breast cancer risk, with the A allele showing significantly elevated frequency in patients (56% vs. 30% in controls) and an odds ratio of 2.97 (P=0.0003).