Yaping Song

Common genetic polymorphisms in pre-microRNAs and risk of cervical squamous cell carcinoma.

MicroRNAs (miRNAs) function as gene regulator and they participate in diverse biological pathways. Common single nucleotide polymorphisms (SNPs) in pre‐microRNAs may change their property through altering miRNAs expression and/or maturation. We conducted a pilot study to test whether SNPs in pre‐microRNAs were associated with cervical squamous cell carcinoma (CSCC). Genotypes of three SNPs in pre‐miRNAs (hsa‐miR‐196a2 rs11614913 C/T, hsa‐miR‐499 rs3746444 A/G, and hsa‐miR‐146a rs2910164 G/C) in 226 CSCC patients and 309 control subjects were determined with the use of PCR‐restriction fragment length polymorphism (RFLP) assay. Significantly increased CSCC risks were found to be associated with G allele of rs3746444 and G allele of rs2910164 (P = 0.017, OR = 1.454, and P = 0.016, OR = 1.355, respectively). Increased CSCC risks were associated with them in different genetic model (P = 0.0004, OR = 1.98 for rs3746444 in an overdominant model, and P = 0.024, OR = 2.10 for rs2910164 in a codominant model, respectively). Results of stratified analyses revealed that rs2910164 is associated with tumor differentiation and lymph node status (P = 0.043, OR = 2.08, and a borderline P = 0.057, OR = 0.41, respectively). No association between rs11614913 and CSCC risk was observed. The present study provides evidence that rs3746444 and rs2910164 are associated with CSCC, indicating that common genetic polymorphisms in pre‐microRNAs contribute to the pathogenesis of CSCC. Mol. Carcinog.

Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy

BACKGROUND Common single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering microRNAs (miRNAs) expression and/or maturation, resulting diverse functional consequences. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with dilated cardiomyopathy (DCM). METHODS Genotypes of 3 SNPs in pre-miRNAs (has-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, hsa-mir-146a rs2910164 C/G) in 221 DCM patients and 321 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay. RESULTS Significantly increased DCM risks were found to be associated with variant allele of has-mir-196a2 rs11614913 C/T (T allele) and hsa-mir-499 rs3746444 A/G (G allele) (P<0.0001, OR=1.730, 95% CI=1.345-2.227, and P<0.0001, OR=1.794, 95% CI=1.350-2.385, respectively). We found that increased DCM risk was statistically significantly associated with these 2 SNPs in a dominant model (P=0.0001 and P<0.0001 for rs11614913 and rs3746444, respectively). No association between DCM risk and hsa-mir-146a rs2910164 C/G was observed (P=0.451, OR=1.102, 95% CI=0.856-1.418). CONCLUSIONS Both the has-mir-196a2 rs11614913 C/T and hsa-mir-499 rs3746444 A/G, but not hsa-mir-146a rs2910164 C/G, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphisms in pre-microRNAs are associated with DCM.

Association between IL17 Polymorphisms and Risk of Cervical Cancer in Chinese Women

Interleukin-17 (IL-17) is a proinflammatory cytokine that is associated with inflammation, autoimmune disorders, and even tumors. Previous studies revealed that a large group of human malignant tumors have abnormally high IL-17 expression. In the present study, we analyzed two single-nucleotide polymorphisms (SNPs) in the IL17A (rs2275913) and IL17F (rs763780) in 311 cervical cancer patients and 463 controls using TaqMan assays. Our results indicated that the frequencies of AA genotype and A allele of rs2275913 were significantly different between the cervical cancer patients and controls (P = 0.008, OR = 1.32, 95% CI, 1.07–1.62). Stratified analyses revealed that the polymorphism of rs2275913 was also associated with positive peritumor intravascular cancer emboli and high clinical stage. The genotype and allele frequencies of rs763780 did not show any difference between patients and controls or relate to patient clinical characteristics. Collectively, these findings suggested that IL17 gene polymorphism rs2275913 was associated with the susceptibility as well as positive peritumor intravascular cancer emboli and high clinical stage of cervical cancer in Chinese women.

A functional insertion/deletion polymorphism in the promoter region of NFKB1 gene increases susceptibility for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China and Southeast Asia. Nuclear factor-kappaB (NF-kappaB)-activation plays critical roles in Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) mediated tumorigenesis in NPC. A functional insertion/deletion polymorphism (-94 insertion/deletion ATTG) in the promoter of NFKB1 gene, which encodes the p50 subunit of NF-kappaB protein complex, was recently identified. This study found that the frequency of ATTG(2) allele in NPC patients was significantly higher than that in control subjects (66% vs. 57.1%, p=0.015, OR=1.453), suggesting that the functional NFKB1 promoter polymorphism is associated with increased risk for NPC.

Functional polymorphism of the NFKB1 gene promoter is related to the risk of dilated cardiomyopathy

BackgroundPrevious studies in experimental and human heart failure showed that nuclear factor kappa B (NF-κB) is chronically activated in cardiac myocytes, suggesting an important involvement of NF-κB in the cardiac remodeling process. A common insertion/deletion (-94 insertion/deletion ATTG, rs28362491) located between two putative key promoter regulatory elements in the NFKB1 gene was identified which seems to be the first potential functional NFKB1 genetic variation. The main goal of the present investigation was to investigate the NFKB1 -94 insertion/deletion ATTG polymorphism in relation to risk of dilated cardiomyopathy (DCM).MethodsA total of 177 DCM patients and 203 control subjects were successfully investigated. The NFKB1 -94 insertion/deletion ATTG polymorphism was genotyped by using PCR-PAGE.ResultsGenotype frequency of NFKB1 -94 insertion/deletion ATTG polymorphism in DCM patients was significantly different from that in control subjects (P = 0.015) and the ATTG2 carrier (ATTG1/ATTG2 + ATTG2/ATTG2) was susceptible to DCM.ConclusionOur data suggested that NFKB1 -94 insertion/deletion ATTG polymorphism is associated with DCM.

Prognostic value of IL-27 polymorphisms and the susceptibility to epithelial ovarian cancer in a Chinese population

This study investigated the association between IL-27 gene polymorphisms and susceptibility to epithelial ovarian cancer in a Chinese population and discusses the risk factors associated with survival time. We collected data on 229 patients diagnosed with epithelial ovarian cancer, from 15 to 77 years of age with a long clinical follow-up period. Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the genotype of IL-27 gene polymorphisms. Ovarian cancer-specific survival (OCSS) according to genotype of IL-27 gene polymorphisms was explored by Kaplan–Meier analysis and Cox proportional hazards modeling. Significant differences for genotype frequencies of both SNP sites were found between cases and controls. Both allele G frequencies were significantly greater among the cases (rs153109: 0.404 vs. 0.303, P = 0.001, odds ratio [OR] = 1.333, 95% confidence interval [CI] = 1.133–1.567; rs17855750: 0.146 vs. 0.083, P = 0.001, OR = 1.766, 95% CI = 1.258–2.481). Haplotype analysis showed haplotypes AG, GT and GG were associated with increased ovarian cancer susceptibility while AT was a protective haplotype. Advanced FIGO stage (stages III + IV) and non-optimal cytoreductive surgery (residual tumor ≥1 cm) were poor prognostic factors in the univariate analysis (P = 0.003, P = 0.049). However, FIGO stage was found to be the only independent significant prognostic factor by Cox proportional hazards analysis (P = 0.042). IL-27p28 mRNA expression was significantly decreased in ovarian cancer patients (P < 0.0001), while no significant relationship was found between IL-27p28 mRNA expression and polymorphism of rs153109 and rs17855750 (P = 0.193 and P = 0.146, respectively). Our study suggests that IL-27 gene polymorphisms may be involved in the susceptibility to epithelial ovarian cancer, but not in survival in a clinic-based Chinese population. Haplotype analysis of these two SNPs seems to be an important mark to predict the disease susceptibility. Advanced FIGO stage, as the only significant, independent risk factor, predicts poor clinical outcomes for patients diagnosed with epithelial ovarian cancer. The decreased expression of IL-27p28 mRNA in ovarian cancer might indicate the antitumor activities of this novel cytokine.

The G894T polymorphism on endothelial nitric oxide synthase gene is associated with increased coronary heart disease among Asia population: Evidence from a Meta analysis

INTRODUCTION Growing studies have revealed the underlying association between eNOS 894G/T (rs1799983) polymorphism and coronary heart disease (CHD) among Asia population. Results from these studies remained conflicting. We conducted this meta-analysis to estimate the overall CHD risk of eNOS 894G/T polymorphism regarding Asia population. MATERIALS AND METHODS Up to October 2011, databases including PubMed, Embase and CNKI (China National Knowledge Infrastructure) were searched to access the relevant genetic association studies. Summary odds ratios and corresponding 95% confidence intervals (CIs) for eNOS 894G/T polymorphism and CHD risk were estimated using fixed or random-effects models when appropriate. RESULTS 18 case-control studies with 2,994 cases and 3,130 controls were available for this study, including 13 studies of East-Asia descendents, 5 studies of Non East-Asian descendents. The mean T allele frequency was 0.111 in the East-Asia population and 0.147 in the Non East-Asia population, respectively. The summary OR for CHD associated with the T allele was 1.52 (95% confidence intervals (95%CI), 1.37-1.69) by random effects model. Similarly, significantly increased risks were observed in the East-Asia population (OR=1.54; 95%CI=1.35-1.76) and in the Non East-Asia population (OR=1.48; 95%CI=1.24-1.77), respectively. CONCLUSIONS This meta-analysis indicated that eNOS 894G/T polymorphism may play an important role in CHD development among Asia population.

Lack of association between TLR4 Asp299Gly polymorphism and atherosclerosis: evidence from meta-analysis

INTRODUCTION Toll like receptor 4 (TLR4) expression was found to increase markedly in human atherosclerotic lesions, notably on macrophages and endothelial cells. TLR4 Asp299Gly polymorphism was associated with a blunted receptor activity and a subsequently diminished inflammatory response, and may subsequently reduce atherosclerosis (AS) risk. However, the results of molecular epidemiological studies remained inconsistent. MATERIALS AND METHODS The PubMed, CNKI databases were searched for all articles available. The OR corresponding to the 95% confidence interval (95% CI) was used to assess the association between TLR4 Asp299Gly polymorphism and risk of AS. RESULTS 15 case-control studies with 9,989 cases and 6,746 controls were available for this analysis. For control subjects, G allele frequency of TLR4 Asp299Gly polymorphism was ranging from 0.045 to 0.085. The G allele and the AG/GG genotypes were not associated with significantly risk of AS (OR=1.02, 95% CI=0.83 - 1.26 for G versus A and OR=0.96, 95% CI=0.80 - 1.15 for AG/GG versus AA, respectively) by random effects model. CONCLUSION These findings indicated that TLR4 Asp299Gly polymorphism may not play a role in AS development.

A functional promoter polymorphism in NFKB1 increases susceptibility to endometriosis.

Numerous proinflammatory cytokines, such as TNFalpha and IL-6, which are nuclear factor kappaB (NF-kappaB) target genes, have been shown to promote proliferation in endometriotic cells, and several other genes involved in promoting growth are also NF-kappaB target genes. The aim of this study was to investigate whether the functional insertion/deletion polymorphism (-94 insertion/deletion ATTG) in the promoter of nuclear factor kappaB gene (NFKB1) is associated with susceptibility to endometriosis. Polymerase chain reaction-polyacrylamide gel electrophoresis method was used to genotype the NFKB1 -94 insertion/deletion ATTG polymorphism in 206 women with endometriosis and 365 ethnicity-matched healthy control women. The genotyping method was confirmed by the DNA sequencing analysis. Genotype at the -94 insertion/deletion ATTG polymorphism in the NFKB1 promoter was in Hardy-Weinberg equilibrium in either case or control subjects. The frequency of the ATTG(2)/ATTG(2) genotype and ATTG(2) allele in the endometriosis was significantly higher than that of control subjects (59.7% vs. 37%, odds ratio = 3.069, p < 0.001 for ATTG(2)/ATTG(2) genotype; 75.2% vs. 59.7%, odds ratio = 2.049, p < 0.001 for ATTG(2) allele), indicating that the -94 insertion/deletion ATTG polymorphism in the NFKB1 promoter was associated with endometriosis. This study suggests that the functional -94 insertion/deletion ATTG polymorphism in the promoter of NFKB1 is associated with an increased risk for endometriosis.

Association of Signal Transducer and Activator of Transcription 3 Gene Polymorphisms with Cervical Cancer in Chinese Women

Signal transducer and activator of transcription (STAT) plays an important role in regulating cell proliferation, differentiation, and apoptosis. Previous studies revealed that abnormal expression/activation of STAT family members were present in a large group of human malignant tumors. In the present study, using polymerase chain reaction (PCR)-restriction fragment length polymorphism, DNA sequencing, and Taqman probe real-time PCR techniques, we analyzed two single-nucleotide polymorphisms (SNPs) in the STAT5B and STAT3 genes (rs6503691 and rs4769793, respectively) in 275 Chinese cervical cancer patients and 340 controls. Our results indicated that the genotype and allele frequencies of SNP rs4769793 were significantly different between the cervical cancer patients and normal subjects (p < 0.05, odds ratio = 1.35, 95% confidence interval = 1. 07-1.70). In addition, stratified analyses revealed that the polymorphism of rs4769793 was also associated with poor tumor differentiation and positive parametrial invasion (p < 0. 05). In contrast, SNP rs6503691 did not show any difference between patients and controls or association with patient clinical characteristics. Collectively, these findings suggested that STAT3 gene polymorphism (rs4769793) was associated with the susceptibility as well as poor differentiation and parametrial invasion of cervical cancer in Chinese women.