Cross-Talk in Mechanomyographic Signals from the Forearm Muscles during Sub-Maximal to Maximal Isometric Grip Force

Purpose

This study aimed: i) to examine the relationship between the magnitude of cross-talk in mechanomyographic (MMG) signals generated by the extensor digitorum (ED), extensor carpi ulnaris (ECU), and flexor carpi ulnaris (FCU) muscles with the sub-maximal to maximal isometric grip force, and with the anthropometric parameters of the forearm, and ii) to quantify the distribution of the cross-talk in the MMG signal to determine if it appears due to the signal component of intramuscular pressure waves produced by the muscle fibers geometrical changes or due to the limb tremor.

Methods

Twenty, right-handed healthy men (mean ± SD: age  = 26.7±3.83 y; height  = 174.47±6.3 cm; mass  = 72.79±14.36 kg) performed isometric muscle actions in 20% increment from 20% to 100% of the maximum voluntary isometric contraction (MVIC). During each muscle action, MMG signals generated by each muscle were detected using three separate accelerometers. The peak cross-correlations were used to quantify the cross-talk between two muscles.

Results

The magnitude of cross-talk in the MMG signals among the muscle groups ranged from, R²_{x, y} = 2.45–62.28%. Linear regression analysis showed that the magnitude of cross-talk increased linearly (r² = 0.857–0.90) with the levels of grip force for all the muscle groups. The amount of cross-talk showed weak positive and negative correlations (r² = 0.016–0.216) with the circumference and length of the forearm respectively, between the muscles at 100% MVIC. The cross-talk values significantly differed among the MMG signals due to: limb tremor (MMG_TF), slow firing motor unit fibers (MMG_SF) and fast firing motor unit fibers (MMG_FF) between the muscles at 100% MVIC (p<0.05, η ² = 0.47–0.80).

Significance

The results of this study may be used to improve our understanding of the mechanics of the forearm muscles during different levels of the grip force.     

Characterization of Lung Function Impairment in Adults with Bronchiectasis

Background

Characteristics of lung function impairment in bronchiectasis is not fully understood.

Objectives

To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy).

Methods

We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence.

Results

In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46–15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52–15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21–18.79, P<0.01) were the major variables associated with FEV₁ being 50%pred or less; and the only variable associated with reduced D_LCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20–17.23, P<0.01). Overall differences in FVC and FEV₁ during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV₁ and D_LCO reduction at baseline.

Conclusion

Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV₁. Changes of other spirometric parameters were less significant during exacerbations.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01761214","term_id":"NCT01761214"}}NCT01761214     

Association between Serum Chemerin Concentrations and Clinical Indices in Obesity or Metabolic Syndrome: A Meta-Analysis

Objective

Chemerin is a novel adipokine. Previous research has investigated the association between chemerin and clinical indices in patients with obesity or metabolic syndrome (MS), although the results obtained have been inconsistent. We conducted a meta-analysis to investigate the association between chemerin and clinical indicators of diabetes, MS and obesity with obesity or MS subjects.

Design and Methods

Studies were identified by searching the PubMed, the Cochrane Library, EMBASE and CNKI, databases beginning with the original report in July 2007 until the end of May 2013. For each variable, summary correlation coefficients were estimated using random-effects or fixed-effect meta-analysis with 95% confidence interval (CI) performed by STATA software.

Results

A total of eight studies with 20 clinical variables (total n = 1787) met the inclusion criteria. The meta-analyse of diabetes markers showed that FSI (r_s = 0.26; 95% CI = 0.21–0.31; P = 0.000), 2HPG (r_s = 0.06; 95% CI = 0.01–0.12; P = 0.030) and HOMA-IR (r_s = 0.178; 95% CI = 0.019–0.337; P = 0.028) were positively correlated with chemerin, however, FPG (r_s = 0.03, 95% CI = −0.02 to 0.08, P = 0.240) and HbA1c (r_s = −0.05; 95% CI = −0.24–0.15; P = 0.641) were not significantly correlated with chemerin. The meta-analyses of MS and obesity markers indicated that TG, TC, CRP BMI, TBF%, WC, WHR and Leptin were positively correlated with chemerin, nevertheless, SBP, DBP, LDL-C, HDL-C, ALT and r-GT were not significantly correlated, adiponectin was negatively correlated. Sensitivity analysis was performed and the summary results did not change significantly.

Conclusions

The results suggest that chemerin in patients with obesity or MS may be associated with obesity, imbalances in lipid and diabetes metabolism and insulin resistance. Chemerin played an important role in the pathophysiology of obesity and MS.     

XPF-673C>T Polymorphism Effect on the Susceptibility to Esophageal Cancer in Chinese Population

Purpose

Xeroderma pigmentsum group F (XPF) plays a pivotal role in DNA nucleotide excision repair and has been linked to the development of various cancers. This study aims to assess the association of XPF genetic variants with the susceptibility to esophageal squamous cell carcinoma (ESCC) in Chinese population.

Methods

This two-stage case-control study was conducted in a total of 1524 patients with ESCC and 1524 controls. Genotype of XPF -673C>T and 11985A>G variants were determined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis was performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI).

Results

Our case-control study showed that XPF -673TT genotype was associated with a decreased risk of ESCC compared with CC genotype in both case-control sets (Tangshan set: OR = 0.58; 95%CI = 0.34–0.99, P = 0.040; Beijing set: OR = 0.66; 95%CI = 0.46–0.95, P = 0.027). Stratified analyses revealed that a multiplicative interaction between -673C>T variant and age, sex or smoking status was evident (Gene-age: P_interaction = 0.002; Gene-sex: P_interaction = 0.002; Gene-smoking: P_interaction = 0.002). For XPF 11985A>G polymorphism, there was no significant difference of genotype distribution between ESCC cases and controls.

Conclusion

These findings indicated that genetic variants in XPF might contribute to the susceptibility to ESCC.     

TERT-CLPTM1L Rs401681 C>T Polymorphism Was Associated with a Decreased Risk of Esophageal Cancer in a Chinese Population

Background

Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90 percent of esophageal cancers. Genetic factors probably play an important role in the ESCC carcinogenesis.

Methods

We conducted a hospital based case-control study to evaluate functional hTERT rs2736098 G>A and TERT-CLPTM1L rs401681 C>T single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction (LDR) method.

Results

When the TERT-CLPTM1L rs401681 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly decreased risk of ESCC (adjusted OR  = 0.74, 95% CI  = 0.58–0.94, p = 0.012); the CT/TT variants were associated with a 26% decreased risk of ESCC (adjusted OR  = 0.74, 95% CI  = 0.59–0.93, P = 0.009). The significantly decreased risk of ESCC associated with the TERT-CLPTM1L rs401681 C>T polymorphism was associated with male sex, young age (<63 years in our study) and alcohol consumption. No association between the hTERT rs2736098 G>A polymorphism and ESCC risk was observed.

Conclusion

TERT-CLPTM1L rs401681 CT and CT/TT genotypes were associated with decreased risk of ESCC, particularly among men, young patients and those reported to be drinkers. However, our results are preliminary conclusions. Larger studies with more rigorous study designs are required to confirm the current findings.     

The MDM2 309T>G Polymorphism and Ovarian Cancer Risk: A Meta-Analysis of 1534 Cases and 2211 Controls

Background

Recently, there have been a number of studies on the association between MDM2 (Murine Double Minute 2) 309 polymorphism and ovarian cancer risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta-analysis to explore more precisely the association between MDM2 309 polymorphism and the risk of ovarian cancer.

Methods

A meta-analysis was performed to examine the association between MDM2 309T>G polymorphism and ovarian cancer risk. Odds ratio (OR) and its 95% confidence interval (CI) were used for statistical analysis.

Results

Our publication search identified a total of 6 studies with 1534 cases and 2211 controls. No significant association was found between MDM2 309T>G polymorphism and ovarian cancer risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Asian subgroup (G vs. T OR = 0.774, 95% CI = 0.628–0.955, P = 0.017, P _het = 0.327; GG vs. TT: OR = 0.601, 95% CI = 0.395–0.914, P = 0.017, P _het = 0.417; dominant model TG+GG vs. TT: OR = 0.661, 95% CI = 0.468–0.934, P = 0.019, P _het = 0.880), and no significant association in any genetic models among Caucasians was observed.

Conclusions

This meta-analysis provides evidence for the association between MDM2 309 polymorphism and ovarian cancer risk, supporting the hypothesis that MDM2 SNP309 G allele acts as an important ovarian cancer protective factor in Asians but not in Caucasians.     

Determinants of the Changes in Glycemic Control with Exercise Training in Type 2 Diabetes: A Randomized Trial

Aims

To assess the determinants of exercise training-induced improvements in glucose control (HbA_1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein content.

Methods

A sub-cohort (n = 35; 48% men; 74% Caucasian) from the HART-D study undertaking muscle biopsies before and after 9 months of aerobic (AT), resistance (RT), or combination training (ATRT).

Results

Changes in HbA_1C were associated with changes in adiponectin (r = −0.45, P = 0.007). Participants diagnosed with type 2 diabetes for a longer duration had the largest increase in PGC-1α (r = 0.44, P = 0.008). Statistical modeling examining changes in HbA_1C suggested that male sex (P = 0.05), non-Caucasian ethnicity (P = 0.02), duration of type 2 diabetes (r = 0.40; P<0.002) and changes in FFA (r = 0.36; P<0.004), adiponectin (r = −0.26; P<0.03), and PGC-1α (r = −0.28; P = 0.02) explain ∼65% of the variability in the changes in HbA_1C.

Conclusions

Decreases in HbA_1C after 9 months of exercise were associated with shorter duration of diabetes, lowering of serum FFA concentrations, increasing serum adiponectin concentrations and increasing skeletal muscle PGC-1α protein expression.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00458133","term_id":"NCT00458133"}}NCT00458133     

Relationship between HbA1c and Continuous Glucose Monitoring in Chinese Population: A Multicenter Study

Objective

Since there is a paucity of reference data in the literature to indicate the relationship between HbA1c, and 24 h mean blood glucose (MBG) from continuous glucose monitoring (CGM) in Chinese populations, we described the above relationship in adult Chinese subjects with different glucose tolerance status.

Methods

Seven-hundred-and-forty-two individuals without history of diabetes were included to the study at 11 hospitals in urban areas across China from 2007–2009 and data of 673 subjects were included into the final analysis. Oral glucose tolerance test (OGTT) classified the participants as nondiabetic subjects, including those with normal glucose regulation (NGR; n = 121) and impaired glucose regulation (IGR; n = 209), or newly diagnosed type 2 diabetes (n = 343). All participants completed testing for HbA1c levels and wore a CGM system for three consecutive days. The 24 h MBG levels were calculated. Spearman correlations and linear regression analyses were applied to quantify the relationship between glucose markers.

Results

The levels of HbA1c and 24 h MBG significantly increased with presence of glucose intolerance (NGR<IGR<type 2 diabetes; both, P<0.001). Analysis of the total population indicated that HbA1c was strongly correlated with 24 h MBG (r = 0.735). The correlation was also found to be significant for the subgroup of participants with newly diagnosed type 2 diabetes (r = 0.694, P<0.001). Linear regression analysis of the total study population yielded the following equation: 24 h MBG _mmol/L = 1.198×HbA1c–0.582 (24 h MBG _mg/dL = 21.564×HbA1c–10.476) (R² = 0.670, P<0.001). The model fit was not improved by application of exponential or quadratic modeling. When HbA1c was 6.5%, the calculated 24 h MBG was 7.2 (6.4–8.1) mmol/L (130 (115–146) mg/dL); and when HbA1c was 7.0%, the 24 h MBG was 7.8 (6.9–8.7) mmol/L (140 (124–157) mg/dL).

Conclusions

Our study provided the reference data of the relationship between HbA1c and CGM in Chinese subjects.     

Association between MLH1 -93G>A Polymorphism and Risk of Colorectal Cancer

Background

The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive.

Objective

The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.

Methods

To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.

Results

The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01–1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01–1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94–3.28; AG versus GG: OR = 1.29, 95% CI = 1.10–1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24–1.68; AA versus AG/GG: OR = 2.29, 95% CI = 1.78–2.96). Egger’s test did not show any evidence of publication bias.

Conclusion

Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.     

Prognostic Significance of Circulating Tumor Cells in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis

Background

The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta-analysis.

Methods

We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies.

Results

A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR]  =  0.88; 95% confidence interval [CI]: 0.59–1.33; Z = –0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18–3.62; Z = 2.20; P = 0.027) and tumor stage (OR  = 1.95; 95% CI: 1.08–3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR]  = 2.19; 95% CI: 1.53–3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR  = 2.14; 95% CI: 1.36–3.38; Z = 3.28; P<0.0001).

Conclusion

The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in lung cancer.     

CpG Island Methylator Phenotype,Helicobacter pylori,Epstein-Barr Virus,and Microsatellite Instability and Prognosis in Gastric Cancer: A Systematic Review and Meta-Analysis

Background

The controversy of CpG island methylator phenotype (CIMP) in gastric cancer persists, despite the fact that many studies have been conducted on its relation with helicobacter pylori (H. pylori), Epstein-Barr virus (EBV), and microsatellite instability (MSI) and prognosis. To drive a more precise estimate of this postulated relationship, a meta-analysis was performed based on existing relevant studies.

Methods

We combined individual patient data from 12 studies which involved 1000 patients with gastric cancer, which met the criteria. We tabulated and analyzed parameters from each study, including H. pylori, EBV, MSI, and clinical information of patients.

Results

The overall OR for H. pylori infection in CIMP positive group vs. negative group revealed that significantly elevated risks of positive H. pylori infection in the former were achieved (OR 2.23 95% CI, 1.25–4.00; P = 0.007, P_{heterogeneity} = 0.05). Similarly, strong relation between EBV infection and CIMP was achieved by OR 51.27 (95% CI, 9.39–279.86; P<0.00001, P_{heterogeneity} = 0.39). The overall OR for MSI in CIMP positive group vs. negative group was 4.44 (95% CI, 1.17–16.88; P = 0.03, P_{heterogeneity} = 0.01). However, there did not appear to be any correlations with clinical parameters such as tumor site, pathological type, cell differentiation, TNM stage, distant metastasis, lymph node metastasis, and 5-year survival.

Conclusions

The meta-analysis highlights the strong relation of CIMP with H. pylori, EBV, and MSI, but CIMP can not be used as a prognostic marker for gastric cancer.     

XRCC1 Arg399Gln Polymorphism Confers Risk of Breast Cancer in American Population: A Meta-Analysis of 10846 Cases and 11723 Controls

Background

In the X-ray repair cross-complementing group 1 (XRCC1) gene, a polymorphism, Arg399Gln (rs25487), has been shown to change neoconservative amino acid and thus result in alternation of DNA repair capacity. Numerous studies have investigated the association between Arg399Gln and breast cancer risk in the American population, but yielding inconsistent results. This study aimed to clarify the role of this polymorphism in susceptibility to breast cancer.

Methods

Literatures were searched in multiple databases including PubMed, Springer Link, Ovid, EBSCO and ScienceDirect databases up to April 2013. A comprehensive meta-analysis was conducted to estimate the overall odds ratio (OR), by integrating data from 18 case control studies of 10846 cases and 11723 controls in the American population.

Results

Overall, significant association was observed between the Arg399Gln polymorphism and breast cancer risk under the random-effects model (OR for dominant model = 1.12, 95% CI: 1.02–1.24, P _{heterogeneity} = 0.003; OR for additive model = 1.07, 95% CI: 1.01–1.14, P _{heterogeneity} = 0.017). Further sensitivity analysis supported the robust stability of this current result by showing similar ORs before and after removal of a single study.

Conclusions

This meta-analysis suggests that the XRCC1 Arg399Gln polymorphism may significantly contribute to susceptibility of breast cancer in the American population.     

Lack of Association between Insulin Receptor Substrate2 rs1805097 Polymorphism and the Risk of Colorectal and Breast Cancer: A Meta-Analysis

Background

Insulin receptor substrate-2 (IRS-2), a signaling adaptor protein, was involved in two cancer-related pathways (the phosphatidylinositol 3′-kinase (PI3K) and the extracellular signal-regulated kinase (ERK) pathways). Several studies have evaluated the association between IRS2 rs1805097 (G>A) polymorphisms and the risk of colorectal and breast cancer. However, the results were inconsistent.

Methodology/Principal Findings

A meta-analysis of seven published case-control studies (4 studies with 4798 cases and 5478 controls for colorectal cancer and 3 studies with 2108 cases and 2507 controls for breast cancer) were conducted to assess the strength of association using crude odd ratios (ORs) with 95% confidence intervals (CIs). For colorectal cancer, no obvious associations were found for all genetic models (homozygote comparison OR = 0.96, 95%CI 0.85–1.08, P_{heterogeneity} = 0.97; heterozygote comparison: OR = 0.91, 95%CI 0.73–1.13, P_{heterogeneity}<0.01; dominant model: OR = 0.92, 95%CI 0.80–1.06, P_{heterogeneity} = 0.05; recessive model: OR = 1.02, 95%CI 0.91–1.14, P_{heterogeneity} = 0.60). In the subgroup analysis by ethnicity, control source and consistency of frequency with Hardy-Weinberg equilibrium (HWE), still no significant associations were observed. For breast cancer, also no obvious associations were found for all genetic models (homozygote comparison: OR = 0.95, 95%CI 0.71–1.26, P_{heterogeneity} = 0.10; heterozygote comparison: OR = 1.00, 95%CI 0.89–1.14, P_{heterogeneity} = 0.71; dominant model: OR = 0.98, 95%CI 0.87–1.10, P_{heterogeneity} = 0.55; recessive model: OR = 0.95, 95%CI 0.72–1.25, P_{heterogeneity} = 0.07). We performed subgroup analyses by sample size and did not find an association.

Conclusions

This meta-analysis indicated that IRS2 rs1805097polymorphism was not associated with colorectal and breast cancer risk.     

The Diagnostic Value of the FIB-4 Index for Staging Hepatitis B-Related Fibrosis: A Meta-Analysis

Background

Liver fibrosis stage is an important factor in determining prognosis and need for treatment in patients infected with hepatitis B virus (HBV). Liver biopsies are typically used to assess liver fibrosis; however, noninvasive alternatives such as the FIB-4 index have also been developed.

Aims

To quantify the accuracy of the FIB-4 index in the diagnosis of HBV related fibrosis and cirrhosis.

Methods

A meta-analysis of studies comparing the diagnostic accuracy of the FIB-4 index vs. liver biopsy in HBV-infected patients was performed using studies retrieved from the following databases: PubMed, Ovid, EMBASE, the Cochrane Library, the Chinese National Knowledge Infrastructure and the Chinese Biology Medicine disc. A hierarchical summary receiver operating curves model and bivariate model were used to produce summary receiver operating characteristic curves and pooled estimates of sensitivity and specificity. The heterogeneity was explored with meta-regression analysis. Publication bias was detected using Egger’s test and the trim and fill method.

Results

12 studies (N = 1,908) and 10 studies (N = 2,105) were included in the meta-analysis for significant fibrosis and cirrhosis, respectively. For significant fibrosis, the area under the hierarchical summary receiver operating curve (AUHSROC) was 0.78 (95% CI = 0.74–0.81). The recommended cutoff value was between 1.45 and 1.62, and the AUHSROC, summary sensitivity and specificity were 0.78 (95% CI = 0.74–0.81), 0.65 (95% CI = 0.56–0.73) and 0.77 (95% CI = 0.7–0.83), respectively. For cirrhosis, the AUHSROC was 0.89 (95% CI = 0.85–0.91). The recommended cutoff value was between 2.9 and 3.6, and the AUHSROC, summary sensitivity and specificity were 0.96 (95% CI = 0.92–1.00), 0.42 (95% CI = 0.36–0.48) and 0.96 (95% CI = 0.95–0.97), respectively. No publication bias was detected.

Conclusions

The FIB-4 index is valuable for detecting significant fibrosis and cirrhosis in HBV-infected patients, but has suboptimal accuracy in excluding fibrosis and cirrhosis.     

CYP11B2 T-344C Gene Polymorphism and Atrial Fibrillation: A Meta-Analysis of 2,758 Subjects

Background

Aldosterone synthase (CYP11B2) T-344C gene polymorphism was found to be correlated with atrial fibrillation (AF) risk. However, the results of individual studies remain conflicting.

Objective and methods

A meta-analysis including 2,758 subjects from six individual studies was performed to explore the correlation between CYP11B2 T-344C gene polymorphisms and AF. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by the fixed– or random–effects model.

Results

A significant relationship between CYP11B2 T-344C gene polymorphism and AF was found under allelic (OR: 1.26, 95% CI: 1.11–1.42, P = 0.0002), recessive (OR: 1.99, 95% CI: 1.26–3.14, P = 0.003), dominant (OR: 0.903, 95% CI: 0.820–0.994, P = 0.036), homozygous (OR: 1.356, 95% CI: 1.130–1.628, P = 0.001), and additive (OR: 1.153, 95% CI: 1.070–1.243, P = 1.0×10⁻¹⁰) genetic models. No significant association between CYP11B2 T-344C gene polymorphism and AF was found under the heterozygous genetic model (OR: 1.040, 95% CI: 0.956–1.131, P = 0.361).

Conclusions

A significant association was found between CYP11B2 T-344C gene polymorphism and AF risk. Individuals with the C allele of CYP11B2 T-344C gene polymorphism have higher risk for AF.     

Genetic Variants in Nitric Oxide Synthase Genes and the Risk of Male Infertility in a Chinese Population: A Case-Control Study

Background

In recent years, oxidative stress has been studied extensively as a main contributing factor to male infertility. Nitric Oxide, a highly reactive free radical gas, is potentially detrimental to sperm function and sperm DNA integrity at high levels. Thus, the aim of this study was to investigate the associations between five polymorphisms in nitric oxide synthase genes (NOSs) and the risk of male infertility and sperm DNA damage as well.

Methods

Genotypes were determined by the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA was measured using immunofluorescence. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using unconditional logistic regression.

Results

Our results revealed a statistically significant difference between the cases and controls in both genotypic distribution (P<0.001) and allelic frequency (P = 0.021) only for the NOS3 rs1799983 SNP. Multivariate logistic regression analyses revealed that rs1799983 was associated with a borderline significantly increased risk of male infertility (GT vs. GG: adjusted OR = 1.30, 95% CI: 1.00–1.70; GT+TT vs. GG: adjusted OR = 1.34, 95% CI: 1.03–1.74; P _trend = 0.020). Moreover, NOS3 rs1799983 was positively associated with higher levels of sperm DNA fragmentation (β = 0.223, P = 0.044). However, the other 4 polymorphisms (NOS1 rs2682826, NOS1 rs1047735, NOS2 rs2297518, and NOS2 rs10459953) were not found to have any apparent relationships with male infertility risk.

Conclusions

Of five NOS gene polymorphisms investigated in the present study, we found NOS3 rs1799983 might cause oxidative sperm DNA damage, thereby contributing to male infertility.     

XRCC3 Thr241Met Polymorphism and Clinical Outcomes of NSCLC Patients Receiving Platinum-Based Chemotherapy: A Systematic Review and Meta-Analysis

Introduction

X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy.

Methods

A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were analyzed.

Results

A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR  = 1.509, 95% CI: 1.099–2.072, P_{heterogeneity}  = 0.618). The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR  = 0.939, 95% CI:0.651–1.356, P_{heterogeneity}  = 0.112) or PFS (MetMet vs. ThrThr, HR  = 0.960, 95% CI: 0.539–1.710, P_{heterogeneity}  = 0.198). Additionally, no evidence of publication bias was observed.

Conclusions

This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS.     

A Genetic Variant in the Promoter Region of miR-106b-25 Cluster Predict Clinical Outcome of HBV-Related Hepatocellular Carcinoma in Chinese

Background

MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients.

Methods

The SNP, rs999885, was genotyped by using the TaqMan allelic discrimination Assay in 414 intermediate or advanced HCC patients. Log-rank test and Cox proportional hazard models were used for survival analysis.

Results

The variant genotypes of rs999885 were associated with a significantly decreased risk of death for intermediate or advanced HCC [additive model: adjusted hazard ratio (HR)  = 0.76,95% confidence intervals (CI)  = 0.59–0.97]. Further stepwise regression analysis suggested that rs999885 was an independently protective factor for the prognosis of HCC in the final model (additive model: adjusted HR  = 0.72, 95% CI  = 0.56–0.91, P = 0.007).

Conclusions

These findings indicate that the A to G base change of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese.     

Replication Study in Chinese Population and Meta-Analysis Supports Association of the 5p15.33 Locus with Lung Cancer

Background

Common genetic polymorphisms on chromosome 5p15.33, including rs401681 in cleft lip and palate transmembrane 1-like gene (CLPTM1L), have been implicated in susceptibility to lung cancer through genome-wide association studies (GWAS); however, subsequent replication studies yielded controversial results.

Methodology and Findings

A hospital-based case-control study in a Chinese population was conducted to replicate the association, and then a meta-analysis combining our non-overlapping new data and previously published data was performed to clearly discern the real effect of lung cancer susceptibility. In our study with 611 cases and 1062 controls, the minor allele T carrier (TT plus CT) group conferred an OR of 0.801 (95% CI = 0.654–0.981) under the dominant model. The meta-analysis comprising 9111 cases and 11424 controls further confirmed the significant association in the dominant model (OR = 0.842, 95% CI = 0.795–0.891). By stratified analysis, we revealed that ethnicity and study design might constitute the source of between-study heterogeneity. Besides, the sensitivity and cumulative analyses indicated the high stability of the results.

Conclusion

The results from our case-control study and meta-analysis provide convincing evidence that rs401681 is significantly associated with lung cancer risk.     

Polymorphisms in ERCC1 and XPF Genes and Risk of Gastric Cancer in an Eastern Chinese Population

Background

Inherited functional single nucleotide polymorphisms (SNPs) in DNA repair genes may alter DNA repair capacity and thus contribute to cancer risk.

Methods

Three ERCC1 functional SNPs (rs2298881C>A, rs3212986C>A and rs11615G>A) and two XPF/ERCC4 functional SNPs (rs2276466C>G and rs6498486A>C) were genotyped for 1125 gastric adenocarcinoma cases and 1196 cancer-free controls by Taqman assays. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate risk associations, and false-positive report probabilities (FPRP) were calculated for assessing significant findings.

Results

ERCC1 rs2298881C and rs11615A variant genotypes were associated with increased gastric cancer risk (adjusted OR = 1.33, 95% CI = 1.05–1.67 for rs2298881 AC/CC and adjusted OR = 1.23, 95% CI = 1.05–1.46 for rs11615 AG/AA, compared with their common genotype AA and GG, respectively). Patients with 2–3 ERCC1 risk genotypes had significant increased risk (adjusted OR = 1.56, 95% CI = 1.27–1.93), compared with those with 0–1 ERCC1 risk genotypes, and this risk was more significantly in subgroups of never drinkers, non-gastric cardia adenocarcinoma (NGCA) and clinical stage I+II. All these risks were not observed for XPF SNPs.

Conclusions

These findings suggest that functional ERCC1 SNPs may contribute to risk of gastric cancer. Larger and well-designed studies with different ethnic populations are needed to validate our findings.