Li Rao

The association of interleukin-16 polymorphisms with IL-16 serum levels and risk of colorectal and gastric cancer

Interleukin (IL)-16, a multifunctional cytokine, plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. Genetic variation in the DNA sequence of the IL-16 gene may lead to altered cytokine production and/or activity, and this variation may modulate an individuals susceptibility to both colorectal cancer (CRC) and gastric cancer (GC). To test this hypothesis, we investigated the association of IL-16 gene polymorphisms with serum levels of IL-16 and the risk of CRC and GC in a Chinese population. We analyzed single-nucleotide polymorphisms of the IL-16 gene in 596 cancer patients (376 patients with CRC and 220 patients with GC), and also in 480 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. Serum IL-16 levels were measured by enzyme-linked immunosorbent assay. The rs11556218 T/G polymorphism of the IL-16 gene was significantly associated with the susceptibility to CRC and GC patients. Both male and female patients carrying the G allele had a significantly higher risk for developing CRC and GC compared with individuals carrying the T allele. Alternatively, women carrying the T allele (rs4072111 C/T) showed a decreased risk for CRC and GC compared with individuals carrying the C allele. In patients with CRC or GC, IL-16 serum levels were significantly higher than those in the healthy controls, although no significant association between IL-16 polymorphisms and serum levels of IL-16 was observed. Our data indicate that IL-16 polymorphisms may contribute to CRC and GC susceptibility.

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.

Null Genotypes of GSTM1 and GSTT1 Contribute to Risk of Cervical Neoplasia: An Evidence-Based Meta-Analysis

Background and Objectives Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens. Methods In this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable. Results The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19–1.65; for GSTT1: OR = 1.30; 95%CI, 1.05–1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18–2.51). Conclusion These findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.

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.

Genetic polymorphism of interleukin-16 and risk of nasopharyngeal carcinoma.

BACKGROUND Common genetic variants in inflammatory cytokine genes can affect the risk of developing nasopharyngeal carcinoma (NPC). Interleukin-16 (IL-16), a pro-inflammatory cytokine, plays a pivotal role in inflammatory diseases as well as in the pathogenesis of tumors. METHODS We analyzed rs4778889 T/C, rs11556218 T/G, and rs4072111 C/T polymorphisms of IL-16 in 206 patients with NPC and 373 healthy controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing methods. RESULTS The rs11556218 T/G polymorphism of IL-16 gene was significantly associated with the susceptibility to NPC. The TG genotype was associated with a significantly higher risk of NPC as compared with the TT genotype (OR=1.67; 95% CI, 1.18-2.36). Patients carrying the G allele had a significantly higher risk for developing NPC compared to individuals carrying the T allele (OR=1.36; 95% CI, 1.03-1.78). CONCLUSIONS This study shows an association between IL-16 gene polymorphisms and the risk of NPC, and our data suggests that IL-16 gene polymorphisms may be useful as genetic susceptibility markers 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.

The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis.

BackgroundEmerging evidence suggests that ataxia telangiectasia-mutated (ATM) is involved in numerous damage repair signaling pathways and cell-cycle checkpoints. Heterozygous carriers of ATM-mutations have an increased risk for the development of breast cancer. The purpose of this study is to evaluate the association between ATM exon39 5557G > A (D1853N, rs1801516) polymorphism and breast cancer susceptibility with the use of a meta-analysis.MethodsBy searching PubMed and Embase databases, a total of 9 epidemiological studies with 4,191 cases and 3,780 controls were identified. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for ATM D1853N polymorphism and breast cancer risk were calculated using fixed- or random-effects model based on the degree of heterogeneity among studies.ResultsNo significant association between the ATM D1853N polymorphism and breast cancer risk was observed in overall analysis (GA versus GG: OR = 1.18; 95% CI, 0.90-1.53; AA versus GG: OR = 0.77; 95% CI, 0.58-1.03; dominant model: OR = 1.16; 95% CI, 0.89-1.51; and recessive model: OR = 0.78; 95% CI, 0.59-1.04, respectively).ConclusionOur results indicate that ATM D1853N polymorphism is not a risk factor for developing breast cancer.

Quantification of chronic aortic regurgitation by vector flow mapping: a novel echocardiographic method

AIMS Quantification of aortic regurgitation (AR) using echocardiography is challenging. A newly established echocardiographic method, vector flow mapping (VFM), can directly measure blood flow volume (FV) regardless of rheological characteristics. We intended to assess the accuracy of VFM in the quantification of chronic AR. METHODS AND RESULTS Twenty-one patients with chronic AR, along with 21 healthy volunteers selected as controls, underwent conventional echocardiography and estimation of aortic blood flow using quantitative Doppler and VFM. The regurgitation ratio (RegR), derived as the quotient of backward and forward aortic FV in the ascending aorta measured by VFM, increased with AR severity: 1.1 +/- 1.5% (normal), 11.4 +/- 3.8% (mild AR), 31.2 +/- 8.0% (moderate AR), and 59.3 +/- 4.7% (severe AR). In a linear regression model, RegR closely correlated with the VC width (r = 0.932) and regurgitation fraction and effective regurgitant orifice measured by the quantitative Doppler method (r = 0.929 and 0.891, respectively). The intra- and interobserver variability of RegR was 4.2 and 6.7%, respectively. There was no difference between RegR measured in the apical five-chamber view and in that in apical three-chamber view using the paired t-test (P = 0.751). CONCLUSION RegR measured by VFM, a new Doppler method allowing quantitative analysis of FV in spite of the presence of turbulent flow, is a highly reproducible parameter with good accuracy for AR quantification.

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.

Circulating level of miR-378 predicts left ventricular hypertrophy in patients with aortic stenosis.

Aims Excessively high left ventricle mass is an independent predictor of adverse prognosis. MicroRNAs (miRs) play crucial roles in the regulation of left ventricle hypertrophy (LVH). However, few circulating miRs have been established as predictors of LVH in aortic stenosis (AS) patients. In this study, we aimed to investigate whether circulating levels of miR-1, miR-133, and miR-378 predict LVH in patients with AS. Methods and Results One-hundred twelve patients with moderate to severe AS and 40 healthy controls were included in the study. Levels of miR-1, miR-133, and miR-378 in the plasma were measured by qPCR. Compared with healthy controls, AS patients had significantly lower circulating levels of miR-1, miR-133, and miR-378. AS patients with LVH had significantly lower miR-378 but not miR-1 and miR-133 compared with those without LVH. Linear regression analysis showed circulating miR-378 had strong correlation with left ventricular mass index (r = 0.283, p = 0.002) and logistic regression showed that lower miR-378 was an independent predictor for LVH in patients with AS (p = 0.037, OR 4.110, 95% CI 1.086 to 15.558). Conclusion Circulating levels of miR-1, miR-133 and miR-378 were decreased in AS patients, and miR-378 predicts LVH independent of the pressure gradient. Further prospective investigations are needed to elucidate whether these circulating miRs affect clinical outcome.