Association between single-nucleotide polymorphisms in pre-miRNAs and the risk of asthma in a Chinese population

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA (miRNA) expression levels or processing and contribute to susceptibility to a wide range of diseases. We investigated the correlation between four SNPs (rs11614913, rs3746444, rs2910164, and rs229283) in pre-miRNAs and the risk of asthma in 220 asthma patients and 540 controls using polymerase chain reaction-restriction fragment length polymorphism methodology and DNA-sequencing. There were significant differences in the genotype and allelic distribution of rs2910164G/C and rs2292832C/T polymorphisms among cases and controls. The CC genotype and C allele of rs2910164G/C were significantly associated with a decreased risk of asthma (CC vs. GG, odds ratio [OR]?= 0.51, 95% confidence interval [CI]: 0.31-0.82; C vs. G, OR = 0.74, 95% CI: 0.59-0.93). Similarly, the TT genotype and T allele of rs2292832C/T were significantly associated with a decreased risk of asthma (TT vs. CC, OR = 0.56, 95% CI: 0.33-0.95; T vs. C, OR = 0.71, 95% CI: 0.53-0.95). However, no significant association between the other two polymorphisms (i.e., rs11614913C/T and rs3746444C/T) and the risk of asthma was observed. Our data indicate that rs2910164G/C and rs2292832C/T may play a role in the development of asthma.     

Association of the Genetic Polymorphisms in Pre-MicroRNAs with Risk of Ischemic Stroke in a Chinese Population

microRNA (miRNA) plays a role in the pathogenesis of ischemic stroke, and single nucleotide polymorphisms in miRNA genes may contribute to disease susceptibility. However, the effect of miR-146a, miR-196a2, and miR-499 polymorphisms on ischemic stroke susceptibility has been rarely reported. Using the TaqMan assay, we evaluated the association of hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913, and hsa-miR-499/rs3746444 polymorphisms with the risk of ischemic stroke in a Chinese population with 531 ischemic stroke patients and 531 control subjects. Rs2910164 C/G genotypes were significantly associated with increased risk of ischemic stroke in different genetic model (homozygote comparison: OR = 2.00, 95% CI, 1.29–3.12, P = 0.002; additive model: OR = 1.35, 95% CI, 1.10–1.65, P = 0.004;dominant model: OR = 1.33, 95% CI, 1.00–1.75, P = 0.049; recessive model: OR = 1.82, 95% CI, 1.20–2.74, P = 0.004). Subjects with allele G of hsa-miR-146a/ rs2910164 also showed increased risk of ischemic stroke (OR = 1.33, 95% CI, 1.09–1.62, P = 0.005). Stratification analysis showed that the association between rs2910164 and the risk of ischemic stroke was more pronounced in subjects over 60 years old, females, non-drinkers, subjects without hypertension or diabetes mellitus. There were significant combined effects between miR-146a/rs2910164 and fasting glucose/low-density lipoprotein cholesterol levels on ischemic stroke susceptibility. However, we failed to find any association between the alleles/genotypes of rs11614913 T/C and ischemic stroke, respectively (P> 0.05). In summary, this study provides evidence that miR-146a/rs2910164 might be associated with a significantly increased risk of ischemic stroke in a Chinese population, and the combined effects between miRNA polymorphism and fasting glucose /blood lipid levels may contribute to stroke pathogenesis.     

Association between microRNA Polymorphisms and Cancer Risk Based on the Findings of 66 Case-Control Studies

MicroRNAs (miRNAs) are small non-coding RNA molecules, which participate in diverse biological processes and may regulate tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to diverse functional consequences, including cancer development, by altering miRNA expression. Numerous studies have shown the association between miRNA SNPs and cancer risk; however, the results are generally debatable and inconclusive, mainly due to limited statistical power. To assess the relationship between the five most common SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs2292832, and miR-27a rs895919) and the risk cancer development, we performed a meta-analysis of 66 published case-control studies. Crude odds ratios at 95% confidence intervals were used to investigate the strength of the association. No association was observed between rs2910164 and cancer risk in the overall group. However, in stratified analysis, we found that either the rs2910164 C allele or the CC genotype was protective against bladder cancer, prostate cancer, cervical cancer, and colorectal cancer, whereas it was a risk factor for papillary thyroid carcinoma and squamous cell carcinoma of the head and neck (SCCHN). Further, rs11614913 was found to be significantly associated with decreased cancer risk, in particular, for bladder cancer, gastric cancer, and SCCHN. For miR-499, a significant association was found between the rs3746444 polymorphism and cancer risk in pooled analysis. In subgroup analysis, similar results were mainly observed for breast cancer. Finally, no association was found between rs2292832 and rs895919 polymorphisms and cancer risk in the overall group and in stratified analysis. In summary, miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 are risk factors for cancer development, whereas mir-149 rs2292832 and miR-27a rs895919 are not associated with cancer risk.     

The Association between Four Genetic Variants in MicroRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and Cancer Risk: Evidence from Published Studies

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development with changes in the microRNA''s properties and/or maturation. Polymorphisms in miRNAs have been suggested in predisposition to cancer risk; however, accumulated studies have shown inconsistent conslusionss. To further validate determine whether there is any potential association between the four common SNPs (miR-196a2C>T, rs11614913; miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the risk for developing risk, a meta-analysis was performed according to the 40 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the extent of the association. The results demonstrated that the rs11614913TT genotype was significantly associated with a decreased cancer risk, in particular with a decreased risk for colorectal cancer and lung cancer, or for Asian population subgroup. In addition, the rs2910164C allele was associated with decreased risk for esophageal cancer, cervical cancer, prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian population subgroup. Similarly, the rs3746444G allele was observed as a risk factor for cancers in the Asian population. It is concluded that two SNPs prsent in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of some cancers, and that the rs3746444 may increase risk for cancer.     

Lack of association between miR-146a rs2910164 C/G locus and colorectal cancer: from a case–control study to a meta-analysis

Previous studies suggested that miR-146a rs2910164 (C/G) locus was predicted to influence the risk of cancer. However, the relationship of miR-146a rs2910164 locus with colorectal cancer (CRC) susceptibility was controversial. We recruited 1003 CRC patients and 1303 controls, and performed a case–control study to clarify the correlation of miR-146a rs2910164 locus with CRC risk. Subsequently, a comprehensive meta-analysis was conducted to verify our findings. In the case–control study, we suggested that miR-146a rs2910164 variants did not alter CRC risk (CG vs. CC: adjusted P=0.465; GG vs. CC: adjusted P=0.436, CG/GG vs. CC: adjusted P=0.387 and GG vs. CC/CG: adjusted P=0.589), even in subgroup analysis. Next, we conducted a pooled-analysis to identify the correlation of miR-146a rs2910164 locus with CRC risk. In this pooled-analysis, 7947 CRC cases and 12,168 controls were included. We found that miR-146a rs2910164 polymorphism did not influence the risk of CRC (G vs. C: P=0.537; GG vs. CC: P=0.517, CG/GG vs. CC: P=0.520 and GG vs. CC/CG: P=0.167). Our findings suggest that miR-146a rs2910164 C/G polymorphism is not correlated with the susceptibility of CRC. In the future, more case–control studies are needed to confirm our results.     

Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population

Background: Common single‐nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre‐miRNAs (miR‐196a2, miR‐146a, and miR‐499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori‐induced gastritis in Japanese population. Methods: The rs11614913 (C>T), rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non‐cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non‐ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases. Results: The rs2910164 CC genotype held a significantly higher risk of GC when compared to non‐cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02–1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non‐cancer and non‐ulcer subjects (OR = 1.39, 95%CI = 1.00–1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09–2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non‐cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0–1 vs 2～, adjusted OR = 1.62, 95%CI = 1.05–2.49, p =.03). Conclusions: The rs2910164 (G>C) SNP in the miR‐146a is associated with susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR‐196a2 is associated with the degree of H. pylori‐induced mononuclear cell infiltration.     

Comprehensive Review of Genetic Association Studies and Meta-Analyses on miRNA Polymorphisms and Cancer Risk

Background

MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444) and cancer risk by using a two-sided meta-analytic approach.

Methods

An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association.

Results

Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC) while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096–1.481, P = 0.002). Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.

Conclusions

The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.     

The Association between Two MicroRNA Variants (miR-499, miR-149) and Gastrointestinal Cancer Risk: A Meta-Analysis

Background

MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Single nucleotide polymorphisms (SNPs) in miRNAs may contribute to cancer susceptibility due to changes in the microRNA’s properties and/or maturation. The present study aimed to investigate the association between two miRNA polymorphisms (miR-499 rs3746444 and miR-149 rs2292832) and gastrointestinal (GI) cancer risk.

Methodology/Principal Findings

We conducted a search of case-control studies in PubMed, Wiley Online Library, Web of Science and the CNKI database. Eleven rs3746444 studies and six rs2292832 studies were included in our meta-analysis. The only obvious association between the miR-499 polymorphism and colorectal cancer susceptibility was found in the homozygote comparison (GG vs. AA: OR = 1.66, 95% CI: 1.02–2.70, P _h = 0.10, P = 0.04). No significant association was found in the subgroup analysis for ethnicity and risk of hepatocellular and gastric cancer. A marginally elevated GI cancer risk was discovered in the recessive model for miR-149 (TT vs. TC+CC: OR = 1.15, 95% CI: 1.03–1.30, P _h = 0.68, P = 0.02). Stratifying the results by ethnicity revealed a slight association between the recessive model and the Asian population (TT vs. TC+CC: OR = 1.14, 95% CI: 1.01–1.29, P _h = 0.79, P = 0.03).

Conclusions/Significance

The present meta-analysis indicates that miR-499 may be associated with the risk to colorectal cancer. MiR-149 may confer a marginally increased risk of susceptibility to gastrointestinal cancer, especially for Asians.     

Effects of common polymorphisms rs2910164 in miR-146a and rs3746444 in miR-499 on cancer susceptibility: a meta-analysis

MicroRNAs (miRNAs) are a class of new non-coding RNA, which may play a more important role in the pathogenesis of human cancers. Rs2910164 in miR-146a and rs3746444 in miR-499 are shown to be associated with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association. We retrieved the relevant articles from PubMed databases. Studies were selected using specific inclusion and exclusion criteria. ORs and 95% CIs were calculated to access the strength of association between microRNA polymorphism and cancer risk. All analyses were performed using the Stata software. Twenty-nine studies were included in this meta-analysis. There were not significant associations between miR-146a rs2910164 and miR-499 rs3746444 polymorphisms with overall cancer risk. In the subgroup analysis by ethnicity, significantly affected cancer risks were found among Asians for both rs2910164 (GC vs. GG: OR = 0.89, 95% CI = 0.82–0.96; CC vs. GG: OR = 0.80, 95% CI = 0.66–0.97; GC + CC vs. GG: OR = 0.86, 95% CI = 0.76–0.97; C vs. G: OR = 0.91, 95% CI = 0.82–1.00) and rs3746444 (GG + AG vs. AA: OR = 1.21, 95% CI = 1.00–1.46). In the tumor type subgroup analysis, rs2910164 C allele decreased the risk of hepatocellular carcinoma (C vs. G: OR = 0.89, 95% CI = 0.80–1.00) and cervical squamous cell carcinoma (C vs. G: OR = 0.72, 95% CI = 0.62–0.84). The rs2910164 in miR-146a and the rs3746444 in miR-499 are likely to be associated with cancer risk.     

Association of pre-microRNAs genetic variants with susceptibility in systemic lupus erythematosus

MicroRNAs (miRNAs) may play important roles in SLE, but genetic polymorphisms of miRNAs and their relationships with various autoantibodies present in SLE patients remain unclear. Here, we report that 213 SLE patients and 209 healthy individuals of Chinese had been taken into this case–control studies, which had been performed by selecting two miRNAs (hsa-mir-146a rs2910164 G>C, and hsa-mir-499 rs3746444 T>C) to analyze the genetic polymorphisms. The single nucleotide polymorphism (SNP) variants had been analyzed by PCR–RFLP and serum anti-ribonucleoprotein (anti-RNP), anti-Sm nuclear antigen (anti-Sm) antibodies had been determined by an anti-ENA kit and serum anti-double-stranded DNA (anti-dsDNA) antibodies had been assessed by indirect immunofluorescence. We found that hsa-mir-146a rs2910164 and hsa-mir-499 rs3746444 polymorphisms had no significant relationship with SLE susceptibility. The genotype frequencies of rs2910164 (GG, CC, and GC) were 16, 37, and 47% in SLE patients, but 11, 39, and 50% in healthy group (P = 0.397), respectively; The genotype frequencies of rs3746444 (CC, TT, and TC) were 3, 74, and 23% in SLE patients, but 3, 76, and 22% in healthy group (P = 0.892), respectively. The G and C allele frequencies of rs2910164 were 39 and 61% in SLE patients, but 36 and 64% in healthy group (P = 0.990), respectively. The C and T allele frequencies of rs3746444 were 15 and 85% in SLE patients, but 14 and 86% in healthy group (P = 0.702), respectively. In addition, we also showed no significant difference in the distribution of rs2910164 and rs3746444 genotypes in each of the three antibodies (anti-RNP, anti-Sm, and anti-dsDNA).     

miR-146a and miR-196a2 Polymorphisms in Patients with Ischemic Stroke in the Northern Chinese Han Population

MicroRNAs are endogenous non-coding RNAs about 22 nucleotides in length that can repress the expression of proteins by binding to the 3′-untranslated regions of target messenger RNAs. We hypothesized that polymorphisms in miR-146a and miR-196a2 are associated with risk of ischemic stroke in the northern Chinese Han population. In a case–control study of 368 ischemic stroke patients and 381 control subjects that were frequency matched by age and gender, we genotyped two single nucleotide polymorphisms (rs11614913 in miR-196a2 and rs2910164 in miR-146a) using polymerase chain reaction-ligation detection reaction. The frequencies of the rs2910164 CC genotype and C allele within miR-146a were not significantly different in patients with ischemic stroke compared with those in the healthy control group. In subgroup meta-analysis, rs2910164 in miR-146a and large-artery atherosclerosis, rather than small-vessel disease, showed the significant association under the dominant model (CC vs CG+GG, OR 1.694; 95 % CI 1.199–2.395 p = 0.003). After adjusting for confounding risk factors of ischemic stroke by logistic regression analysis, this significant correlation remained. In addition, the distributions of the miR-196a2 genotypes and alleles were not statistically different between ischemic stroke and healthy groups. We also did not find any significant association from stroke subtypes. The CC genotype and C allele of rs2910164 within miR-146a are associated with an increased incidence of large-artery athersclerotic stroke in the northern Chinese Han population. This study indicates that miR-146a (rs2910164) might contribute to ischemic stroke susceptibility in the northern Chinese Han population.     

Gene Polymorphisms of Micrornas in Helicobacter pylori-Induced High Risk Atrophic Gastritis and Gastric Cancer

Background and aims

MicroRNAs (miRNAs) are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC) and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of GC or high risk atrophic gastritis (HRAG) in European population.

Methods

Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281) of European descent. MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR.

Results

Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR) - 1.46, 95% confidence interval (CI) 1.03-2.07, P = 0.032). MiR-608 GG genotype was more frequent in GC when compared to controls (OR −2.34, 95% CI 1.08–5.04), but significance remained marginal (P = 0.029). A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14–5.22, P = 0.021). The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC.

Conclusions

Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European subjects.     

A functional variant of pre-miRNA-196a2 confers risk for Behcet’s disease but not for Vogt–Koyanagi–Harada syndrome or AAU in ankylosing spondylitis

This study aimed to investigate the predisposition of common pre-miRNA SNPs with Behcet’s disease (BD), Vogt–Koyanagi–Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS). A two-stage association study was carried out in 859 BD, 400 VKH syndrome, 209 AAU⁺AS⁺ patients and 1,685 controls all belonging to a Chinese Han population. Genotyping, the expression of miR-196a and Bach1 (the target gene of miR-196a), cell proliferation, cytokine production were examined by PCR–RFLP, real-time PCR, CCK8 and ELISA. In the first stage study, the results showed significantly increased frequencies of the miR-196a2/rs11614913 TT genotype and T allele in BD patients (adjusted P _c = 0.024, OR = 1.63; adjusted P _c = 5.4 × 10^?3, OR = 1.45, respectively). However, no significant association of the tested SNPs with VKH and AAU⁺AS⁺ patients was observed. The second stage and combined studies confirmed the association of rs11614913 with BD (TT genotype: adjusted P _c = 6×10^?5, OR = 1.53; T allele: adjusted P _c = 8×10^?6, OR = 1.35; CC genotype: adjusted P _c = 0.024, OR = 0.68). A stratified analysis showed an association of the rs11614913 TT genotype and T allele with the arthritis subgroup of BD (P _c = 5.3 × 10^?3, OR = 1.89; P _c = 0.015, OR = 1.56, respectively). Functional experiments showed a decreased miR-196a expression, an increased Bach1 expression and an increased production of IL-1β and MCP-1 in TT cases compared to CC cases (P = 0.023, P = 0.0073, P = 0.012, P = 0.002, respectively). This study shows that a functional variant of miR-196a2 confers risk for BD but not for VKH syndrome or AAU⁺AS⁺ by modulating the miR-196a gene expression and by regulating pro-inflammatory IL-1β and MCP-1 production.     

Three common functional polymorphisms in microRNA encoding genes in the susceptibility to hepatocellular carcinoma: A systematic review and meta-analysis

Emerging evidences have shown that common genetic polymorphisms in microRNAs may be associated with the development of hepatocellular carcinoma (HCC); but individually published studies and previous meta-analyses revealed inconclusive results. The aims of this review and meta-analysis are to assess whether common single-nucleotide polymorphisms (SNPs) in the genes encoding the microRNAs are associated with susceptibility to HCC development and clinicopathologic characteristics of hepatitis B virus (HBV) related HCC. A computerized search was performed in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases to identify relevant articles published before January 1st 2013. Ten case–control studies were assessed with a total of 3437 cases and 3437 healthy controls. Three common functional SNPs in miRNA-encoding genes were found, including miR-146a G > C (rs2910164), miR-196a-2 C > T (rs11614913) and miR-499 T > C (rs3746444). This meta-analysis revealed that the miR-146a*C variant was associated with a decrease in HCC risk, especially among Asian and male populations; while the miR-196a-2*T variant was associated with susceptibility to HCC among Caucasian populations. However, we failed to find any significant correlations between the miR-499*C polymorphism and HCC risks. When further stratification on HBV status was conducted, a similar trend of association between the three SNPs and the HBV-related HCC risks was observed, but these results were not statistically significant due to small sample sizes. The current meta-analysis demonstrates that SNPs contained in the genes encoding miR-146a and miR-196a-2 may play a major role in genetic susceptibility to HCC.     

Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies

Background

MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results.

Methodology/Principal Findings

We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR = 1.18, 95% CI = 1.03–1.34, P<0.001 for heterogeneity test). In the stratified analyses, we observed that the CC genotype might modulate breast cancer risk (OR = 1.11, 95%CI = 1.01–1.23, P _{heterogeneity} = 0.210) and lung cancer risk (OR = 1.25, 95%CI = 1.06–1.46, P _{heterogeneity} = 0.958), comparing with the TC/TT genotype. Moreover, a significantly increased risk was found among Asian populations in a dominant model (TC/CC versus TT, OR = 1.24, 95% CI = 1.07–1.43, P _{heterogeneity} = 0.006).

Conclusions

These findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers.     

Single nucleotide polymorphism rs11614913 associated with CC genotype in miR-196a2 is overrepresented in laryngeal squamous cell carcinoma,but not salivary gland tumors in Polish population

The miRNA-196a2 has shown significance in the development of various neoplasms, including head and neck squamous cell carcinoma (HNSCC). The oncogenic functionality of this miRNA is mediated via its potential to target annexin A1 mRNA, a tumor suppressor gene involved in inhibition of the NF-κB pathway. Interestingly, recent data indicate a susceptibility for aforementioned neoplasms in patients with the CC genotype vs the CT and TT genotypes of the rs11614913 SNP located within the DNA sequence of the miR-196a2 that results in elevated expression of the gene. To further investigate this phenomenon, we genotyped this SNP in 40 patients with laryngeal squamous cell carcinoma (LSCC), the most common tumor of the head and neck region and 60 patients with salivary gland tumors (SGT) that show a yet unexplained incidence increase in the last two decades. In agreement with previous reports, we have identified a statistically significant (p?<?0.05) overrepresentation of the CC genotype in LSCC patients and demonstrated in LSCC cell lines that it results in elevated expression of miR-196a2 as compared to cell lines with the TT genotype of the respective SNP. Importantly, none of these correlations was found in patients with SGT. These findings underline the importance of the SNP rs11614913 for LSCC development in the Polish population and moreover highlight the different genetic background of the two studied neoplasms of the head and neck region.     

Association study of single nucleotide polymorphisms in pre-miRNA and rheumatoid arthritis in a Han Chinese population

The aim of this study was to perform an association study between two single nucleotide polymorphisms (SNPs) rs2910164 G>C and rs3746444 T>C in pre-miRNA (hsa-mir-146a and hsa-mir-499) and rheumatoid arthritis (RA) in the Han Chinese population. 208 Han Chinese patients with RA and 240 healthy controls were recruited in this study. The SNPs was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Anti-cyclic citrullinated peptide (anti-CCP) antibody was measured by enzyme linked immunosorbent assay and rheumatoid factor (RF) was measured by rate nephelometry. The genotype frequencies between cases and controls were compared by χ(2) analysis. No significant association between the SNPs (rs2910164 and rs3746444) and RA was observed (P = 0.631 and 0.775, respectively), and the SNPs did not show any association with the RF-positive (P = 0.631 and 0.775, respectively). However, there was a significant difference on the level of anti-CCP antibody between different genotypes in rs3746444 (P = 0.007). The heterozygote CT had significantly higher level of anti-CCP antibody compared with homozygote CC and TT (P = 0.054 and 0.003, respectively). We first investigated the association between the SNPs (rs2910164 G>C and rs3746444 T>C) in the pre-miRNA (hsa-mir-146a and hsa-mir-499) and RA in a Han Chinese population. We did not find a significant association between the SNPs and the susceptibility to RA, while the SNP rs3746444 may affect anti-CCP antibody production.