Archives of Medical Research - Articles in Press

Contribution of NAD(P)H Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and Risks of Colorectal Adenoma and Cancer for Caucasians: A Meta-analysis - Uncorrected Proof

Jing Chen, Yuan Lin, Ru Zhang, Zhi-jie Huang, Xing-guo Pan — 2012-02-03

Background and Aims: The effects of polymorphism of NAD(P)H quinone oxidoreductase 1 (NQO1 Pro187Ser, rs1800566) on the risks of colorectal adenoma and cancer have been widely studied and results remain controversial. Therefore, the aim of this meta-analysis was to quantitatively assess the relationships.Methods: Databases of Medline, Embase and Wanfang were retrieved until May 15, 2011. Pooled odds ratio (OR) and 95% confidence interval (95% CI) as effect sizes were calculated by using fixed- or random-effect model. Cochrane Q-test was used to explore between-study heterogeneity; p <0.10 indicated statistical significance.Results: A total of 12 case-control studies with 11,700 individuals (including 5528 cases and 6172 controls) were included in this meta-analysis. Of these studies, four studies conducted in Caucasian populations were for colorectal adenoma, and eight studies were for colorectal cancer. NQO1 187Ser allele was significantly associated with increased risk of colorectal adenoma in co-dominant and dominant comparison models (OR = 1.07, 95% CI = 1.04–1.32 for ProSer vs. ProPro and OR = 1.19, 95% CI = 1.06–1.33 for Ser carries vs. ProPro), without between-study heterogeneity. Overall, NQO1 Pro187Ser was not associated with risk of colorectal cancer, without between-study heterogeneity. Subgroup analyses indicated that Ser allele was significantly associated with increased risk of colorectal cancer for Caucasians (OR = 1.14, 95% CI = 1.00–1.30 for ProSer vs. ProPro and OR = 1.16, 95% CI = 1.02–1.31 for Ser carries vs. ProPro).Conclusions: This meta-analysis suggested that Ser allele of NQO1 Pro187Ser significantly contributed to the increased risks of colorectal adenoma and cancer in Caucasians.

Number of Microparticles Generated During Acute Myocardial Infarction and Stable Angina Correlates with Platelet Activation - Uncorrected Proof

2012-02-03

Background and Aims: Elevated levels of circulating microparticles (MPs) have been reported in patients with acute myocardial infarction (AMI) and coronary artery disease. Platelet activation and inflammation have been recognized during AMI and stable angina (SA). We hypothesize that the origin and count of MPs in AMI and SA patients are related to markers of inflammation and platelet activation.Methods: Platelet, monocytes and endothelial MPs and surface P-selectin were determined in 12 AMI patients, 10 SA patients and 9 controls by flow cytometry. Plasma P-selectin, CD40 ligand (sCD40L) and interleukin 6 (IL-6) levels were evaluated by ELISA methods.Results: The total MP count was compared in control subjects, AMI, and SA patients: 12 765 (8 465) vs. 38 750 (11 931) vs. 29 715 (12 072) counts/μl (p = 0.01), respectively. Patients with AMI displayed higher levels of total and platelet origin- tissue factor-positive (CD42/CD142) MPs than patients with SA: 72.8 (6.2) vs. 56.2 (6.4) %, p = 0.001. Levels of soluble P-selectin were significantly elevated in patients with AMI as compared to SA patients: 146 (6.5) vs. 107 (2.7) ng/mL, p = 0.005; significant correlation between total MP count and relative number of CD34, CD51, CD42-positive MPs, and the P-selectin expression was observed in patients with AMI.Conclusions: Platelet activation in AMI is associated with increased generation of MPs not only from platelets, but also monocytes and endothelial cells. It suggests that interactions between platelets, monocytes and endothelial cells play an important role in the pathogenesis of myocardial ischemia.

Plasma Lipoprotein-associated Phospholipase A2 Is Inversely Correlated with Proprotein Convertase Subtilisin-kexin Type 9 - Uncorrected Proof

2012-02-01

Background and Aims: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a pro-atherogenic phospholipase A2, which is predominantly complexed to low-density lipoprotein (LDL) particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation. We determined relationships between plasma PCSK9 and Lp-PLA2 mass.Methods: Lp-PLA2 mass (turbidimetric immunoassay), PCSK9 (enzyme-linked immunosorbent assay) and (apo) lipoproteins were measured in 53 nondiabetic subjects (27 women) with body mass index <30 kg/m2.Results: Lp-PLA2 and PCSK9 levels were both correlated positively with LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol (r = 0.330 to r = 0.382, p ≤0.02). Remarkably, Lp-PLA2 was inversely related to PCSK9 (r = −0.388, p = 0.004). The Lp-PLA2/apolipoprotein B ratio, as a measure of the Lp-PLA2 content in apolipoprotein B-containing lipoproteins, was also inversely correlated with PCSK9 (r = −0.575, p <0.001). The inverse relationships of Lp-PLA2 (p = 0.023) and the Lp-PLA2/apolipoprotein B ratio (p = 0.001) with PCSK9 levels remained significant after controlling for age, gender, triglycerides and HDL cholesterol.Conclusions: Despite increasing effects on LDL cholesterol, higher PCSK9 levels are unlikely to confer impaired Lp-PLA2 metabolism. We propose to evaluate the possible influence of PCSK9 inhibiting strategies on Lp-PLA2 regulation and vice versa to determine effects of Lp-PLA2 inhibitors on the PCSK9 pathway.

Identification of the Mutations in the Tissue-nonspecific Alkaline Phosphatase Gene in Two Chinese Families with Hypophosphatasia - Uncorrected Proof

2012-02-01

Background and Aims: Hypophosphatasia is a genetic disorder characterized by defective bone and tooth mineralization and a deficiency of serum and bone alkaline phosphatase activity. To date, few studies have identified gene mutations in Chinese patients with hypophosphatasia. We sought to characterize the clinical manifestations and identify the mutations associated with the disease in Chinese hypophosphatasia patients.Methods: All 12 exons and the exon-intron boundaries of the ALPL gene were amplified and directly sequenced in two probands from unrelated Chinese families. The mutation sites were identified in other unaffected members of these two families and 100 healthy controls.Results: In family 1, the proband displayed one novel splice site mutation, c.298-1G>A, which consisted of a homozygous G>A transition at nucleotide 298-1 in intron 4. The proband’s mother displayed the heterozygous G/A ALPL gene mutation, but her father was identified as G/G homozygous. A paternity test ruled out false paternity and therefore confirmed that this splicing mutation occurred de novo either in the paternal germline or in the early development of the patient. In family 2, the proband revealed a novel missense mutation (c.1271T>C) in exon 11, which resulted in p.Val424Ala in the mature ALPL polypeptide. Furthermore, c.298-1G>A and c.1271T>C mutations were not found in unaffected family members of these two Chinese families and 100 unrelated controls.Conclusions: Our study shows that the novel de novo splicing mutation c.298-1G>A in intron 4 and the missense mutation c.1271T>C in exon 11 of the ALPL gene are responsible for hypophosphatasia in some Chinese patients.

Production of IL-10, TNF and IL-12 by Peripheral Blood Mononuclear Cells in Mexican Workers Exposed to a Mixture of Benzene-Toluene-Xylene - Uncorrected Proof

2012-02-01

Background and Aims: Occupational exposure to low-level benzene and the joint action of toluene-xylene probably cause effects on circulating monocytes immune response. We undertook this study to determine relationship between occupational exposure to benzene-toluene-xylene mixture (BTX) and IL-10, TNF and IL-12 production by peripheral blood mononuclear cells.Methods: Exposure was estimated in 54 workers from a paint company in Mexico City through BTX accumulated potential dose (BTX-APD). Two exposure groups were formed: high and low BTX-APD established with a cutoff point at ≥1.0 of BTX-APD, as a function of the geometric mean of the estimator’s value distribution and the higher agreement between BTX-APD ≥1.0 and the areas referred as using (or not) organic solvents in the work process. IL-10, TNF and IL-12 concentrations were measured with ELISA. Through multiple linear regression models, the production of each of the proposed cytokines and of the whole set was assessed.Results: Workers with high BTX-APD showed a significant reduction in TNF production (β = −1,196.0 pg/mL; p = 0.01); a reduction for IL-10 (β = −520.3; p = 0.13) and IL-12 (β = −843.3; p = 0.09) was also observed, although without statistical significance.Conclusions: TNF production assessed in workers with a high BTX-APD is lower than in those with a low BTX-APD, but not in IL-10 and IL-12 production.

Serum Chemokines RANTES and Monocyte Chemoattractant Protein-1 in Egyptian Patients with Atopic Asthma: Relationship to Disease Severity - Uncorrected Proof

Sahar Saad-El-Din Bessa, Gehan Hassan Abo El-Magd, Maaly Mohamed Mabrouk — 2012-02-01

Background and Aims: Asthma is a highly prevalent, complex inflammatory disease of the airways often associated with bronchial hyperreactivity and atopy. The chemokine RANTES (regulated upon activation, normal T -cell expressed and secreted) is an important element for the chemotaxis at the site of allergic inflammation. This study aimed to assess the serum levels of the chemokines RANTES and monocyte chemoattractant protein-1 (MCP-1) in Egyptian patients with atopic asthma and to evaluate their possible relation t the severity of airway obstruction.Methods: The study included 60 Egyptian patients with atopic asthma and 20 healthy volunteers. Serum levels of the chemokines RANTES and MCP-1 were measured. Total serum IgE level and absolute eosinophil counts were determined. The severity of airway obstruction was assessed using spirometric measurement (FEV1).Results: The serum levels of RANTES were significantly higher in all asthmatic patients than the controls (p <0.001). Moreover, RANTES levels were significantly increased in patients with moderate and severe asthma as compared to those with mild asthma (p <0.001). Serum RANTES correlated positively with absolute eosinophil counts and total serum IgE and negatively with FEV1, whereas there was no significant correlation with serum MCP-1 in all asthmatic patients.Conclusions: Serum RANTES may be used as a useful noninvasive marker of airway obstruction and a potential diagnostic tool for monitoring asthma severity. In this regard, identification and blocking of this chemokine and/or its receptor may be a promising therapeutic approach to asthmatic patients.

Therapeutic Potential of Motor Neurons Differentiated from Embryonic Stem Cells and Induced Pluripotent Stem Cells - Uncorrected Proof

Rodrigo López-González, Iván Velasco — 2012-01-30

Abstract: Degeneration of motor neurons (MN) caused by disease or injury leads to paralysis and is fatal in some conditions. To date, there are no effective treatments for MN disorders; therefore, cell therapy is a promising strategy to replace lost MN. Embryonic stem (ES) cells isolated from the inner cell mass of mammalian blastocysts self-renew and are pluripotent because they differentiate into cell types of the three germinal layers. Reprogramming of adult cells to a state similar to ES cells, termed induced pluripotent stem (iPS) cells has been recently reported. It is well established that pluripotent cell types can give rise to specialized phenotypes, including neurons. Mouse, monkey and human MN can be differentiated from ES and iPS cells using procedures generally involving embryoid bodies formation and stimulation with retinoic acid and sonic hedgehog. Differentiated MN express characteristic molecular markers such as Islet1, HB9 and choline acetyltransferase, exhibit electrophysiological maturity and are able to form synaptic contacts similar to neuromuscular junctions in vitro. Furthermore, transplanted MNs promote functional recovery in animal models of neurodegenerative diseases and MN injury. The potential clinical applications of stem cell-derived MNs was enhanced after iPS cell derivation, which makes possible the generation of patient-specific pluripotent cells for autologous cell replacement therapies and may be used for drug development and disease modeling. This review summarizes MN differentiation protocols from ES and iPS cells in regard to neuronal differentiation efficiency, expression of MN markers and functional properties in vitro, as well as their therapeutic effects after grafting.

REVIEWERS 2011 - Uncorrected Proof

2012-01-24

The Editors of Archives of Medical Research extended their appreciation to the following reviewers for their assistance during 2011: Adriana Aguilar-Lemarroy, Mexico

Association of Serum Lipid/Lipoprotein with Pro12Ala Polymorphism in PPAR-γ2 Among Chinese Nonagenarians/Centenarians - Uncorrected Proof

2012-01-24

The authors would like to revise the authorship for their article in Archives of Medical Research 42 (2011) 613-619. The revised authorship should be Gang Cheng,a,∗ Hui Wang,b,∗ Huacong Deng,a Changquan Huang,b and Qingxiu Liub

Prevalence of Obesity and Overweight in Children: A Study in Government Primary Schools in the City of Rabat, Morocco - Uncorrected Proof

2012-01-05

Background and Aims: We undertook this study to assess the prevalence of obesity and overweight in children enrolled in government primary schools in the city of Rabat, Morocco.Methods: Twenty three schools were randomly selected. A cross-sectional study was conducted between April 2010 and June 2010. The survey was conducted on the basis of two questionnaires for both parents and children. The references used are those of the WHO (2007).Results: Our study involved a sample of 1570 children with an average age of 9.7 ± 0.95 years. The prevalence of overweight and obesity was 8.7%. Overweight affected 5.1% and obesity affected 3.6%. The majority of our population consisted of children of low socioeconomic status where 59% of fathers are laborers and 85% of mothers are unemployed.Conclusion: Overweight and obesity do not spare the most underprivileged social strata of our country. Therefore, prevention strategies and programs to raise awareness of risks and threats involved must be a public health priority.

Influenza Vaccine and Healthcare Workers - Uncorrected Proof

2012-01-05

Background and Aims: We undertook this study to review attitudes, beliefs and practices of healthcare workers (HCW) toward pandemic influenza A vaccine (H1N1) 2009 reported in the literature.Methods: Relevant papers published from 2009–2011 reporting attitudes, beliefs and practices of HCW towards pandemic influenza vaccine were identified. Variables such as age, gender, profession, work place area, and previous vaccination uptake were analyzed.Results: In this study, 30 articles regarding attitudes and beliefs toward pandemic influenza vaccination, vaccine uptake and intention to accept vaccine were analyzed. Most studies were cross-sectional in design. Vaccination intention and uptake varies among different countries, 13.5–89.0% and 7.5–63.0%, respectively. Most common reasons for rejection were fear of adverse events, doubt regarding efficacy, not feeling as belonging to a high-risk group and believing that influenza is not a serious illness. Physicians show more favorable attitudes compared to nurses. The main predictor of vaccine uptake was having received previous influenza vaccination.Conclusions: Pandemic influenza uptake was low in most countries. The main reason among HCW for rejection was concern regarding side effects. It is necessary to establish educational programs to provided reliable information and raise awareness of HCW about vaccine use so that they can act as vaccine promoters among the general population.

Human Immunodeficiency Virus Is the Major Determinant of Steatosis and Hepatitis C Virus of Insulin Resistance in Virus-associated Fatty Liver Disease - Uncorrected Proof

2012-01-05

Background and Aims: To promote our understanding of the relative contribution of metabolic and viral factors, the independent predictors of fatty liver and insulin resistance (IR) were assessed by comparing patients with nonalcoholic fatty liver disease (NAFLD) to individuals with virus-associated fatty liver disease (VAFLD): human immunodeficiency virus (HIV)-VAFLD, hepatitis C virus (HCV)-VAFLD and HIV-HCV-VAFLD.Methods: One hundred eighty eight consecutive patients with viral infections (103 HIV, 85 patients with HCV genotype 1 infection: 45 mono-infected and 40 HIV/HCV co-infected) with or without steatosis and 126 NAFLD patients were analyzed. Steatosis was diagnosed by ultrasonography. To assess the odds ratio (OR) of steatosis and IR, HCV and NAFLD, respectively, were used as the reference values. IR was evaluated through homeostasis model (HOMA) and the metabolic syndrome (MetS) using standard criteria.Results: The prevalence of VAFLD was 47%. Multivariate logistic regression analysis was carried out using HCV as the reference. VAFLD was predicted by HIV, HIV/HCV, female gender, waist circumference (WC) and HOMA (OR = 3.99, 3.76, 2.80, 1.08 and 1.18). According to multiple linear regression using NAFLD as a reference, IR was predicted by HCV, HIV and HIV/HCV, WC, triglycerides (coefficient beta = 2.25, 0.99, 1.86, 0.08, 0.05, respectively). In linear models, for any given number of components of MetS, HCV and HCV/HIV-associated fatty liver disease had greater HOMA compared to NAFLD (p <0.001).Conclusions: Whereas HIV confers a higher risk of steatosis, VAFLD is associated with higher IR than NAFLD and such an effect is specifically linked to HCV rather than to HIV infection.

Anti-quorum Sensing and Antibiofilm Potential of Capparis spinosa - Uncorrected Proof

2012-01-04

Background: Emergence of antibiotic resistance among bacterial pathogens often leads to the failure of existing antibiotics to treat bacterial infections; thus, there is a need to seek alternative treatment measures. The aim of this study was to evaluate the anti-quorum sensing (anti-QS) and antibiofilm potential of Capparis spinosa to prevent the onset of bacterial infections as an alternate to antibiotics.Methods: The methanolic extract of the dried fruits of C. spinosa was assessed for its activity in inhibiting QS depended phenomenon such as violacein pigment production in Chromobacterium violaceum, biosurfactant production in Pseudomonas aeruginosa PAO1, swimming and swarming motility, exopolysaccharide production (EPS), and biofilm formation in Esherichia coli, Proteus mirabilis, Serratia marcescens and PAO1.Results: Extract of C. spinosa showed a higher degree of anti-QS activity in a dose dependent manner without affecting the bacterial growth. At 2 mg/mL, this extract significantly (p ≤0.005) inhibited the biofilm formation to 79, 75, 73, 70% and EPS production to 58, 46, 66, and 67% in S. marcescens, PAO1, E. coli and P. mirabilis, respectively. It also exhibited inhibition in swimming and swarming motility of bacterial pathogens. The non-enzymatic nature of the anti-QS compound in C. spinosa was confirmed by proteinase K and heat treatment.Conclusions: As the methanolic extract of C. spinosa demonstrated anti-QS and antibiofilm activity at 0.5–2 mg/mL, it could be further exploited for novel molecules to treat the emerging infections of antibiotic resistant bacterial pathogens.

Detection of Helicobacter pylori and cagA gene in Nasal Polyps and Benign Laryngeal Diseases - Uncorrected Proof

2012-01-04

Background and Aims: Helicobacter pylori is the most common etiological factor of chronic infection worldwide. It has also been found in human dental plaques, mouth, saliva, tonsils and adenoid tissue, medial ear or nasal polyps and sinuses mucosa, as well in several benign and malignant lesions of the larynx and pharynx. The aim of the study was to investigate the association of H. pylori colonization in chronic rhinosinusitis and benign laryngeal diseases.Methods: The prospective, controlled study involved a series of 30 patients with nasal polyps and normal nasal mucosa and 30 patients with benign laryngeal diseases. Samples of 10–15 mg obtained from fresh tissues were used for nucleic acid purification. All samples were subjected to H. pylori ureA detection by the PCR H. pylori diagnostic test. Samples that were positive for ureA H. pylori gene were evaluated for cagA H. pylori gene.Results: H. pylori DNA (ureA gene) was detected in all patients with nasal polyps, concha bullosa and laryngeal diseases. Presence of H. pylori cagA gene was identified in 7 (23.3%) of 30 patients of H. pylori-positive larynx samples and no positive result was observed in nasal polyps and concha bullosa.Conclusions: Our results reveal the presence of H. pylori DNA in nasal polyps, concha bullosa and benign larynx diseases. cagA-positive H. pylori was observed only in laryngeal tissues. These results may have implications for a possible role of H. pylori in laryngeal diseases.

MTHFR C677T Polymorphism and its Relation to Myocardial Infarction in the Eastern Black Sea Region of Turkey - Uncorrected Proof

Fahri Uçar, Şükrü Çelik, Burcu Yücel, Mehmet Sönmez, Figen Celep, Nergiz Erkut — 2012-01-04

Background and Aims: An association of homozygous MTHFR 677T genotypes with elevated plasma homocysteine level has been documented, but results are still controversial. We aimed to investigate prevalence of the C677T polymorphism in patients with acute myocardial infarction (MI) in the Eastern Black Sea region of Turkey.Methods: We studied genomic DNA of 231 unrelated patients (aged 59 ± 13 years; 175 male, 56 female) with first anterior acute MI and 242 healthy controls (aged 54 ± 19 years; 182 male, 60 female) using real-time polymerase chain reaction kits for the MTHFR C677T mutation.Results: Prevalence of MTHFR C677T mutant genotype was 49.1% (CT: 45.8%, TT: 3.3%) in controls and 48.45% (CT: 38.5%, TT: 9.95%) in patients with acute MI. The TT mutation was more frequent in patients with acute MI than in controls (9.95 vs. 3.3%) (OR; 3.23, 95% CI; [1.34–8.05], p = 0.003).Conclusions: The MTHFR gene homozygote TT mutation is a risk factor for patients with MI in the eastern Black Sea Turkish Population.

Lower Serum Paraoxonase-1 Activity Is Related to Linoleic and Docosahexanoic Fatty Acids in Patients with Type 2 Diabetes - Uncorrected Proof

2012-01-04

Background: Serum paraoxonase-1(PON-1) activity is decreased in clinical conditions associated with low high-density lipoprotein cholesterol (HDL-C), increased lipid peroxidation and low-grade chronic inflammation, as in type 2 diabetes mellitus (T2DM). Until now there are no data about the association of any fatty acid (FA) with PON-1 activity in T2DM.Methods: Twenty patients with T2DM and 16 healthy controls were included in this cross-sectional study. Serum PON-1 activity, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity as well as plasma glucose, HbA1c, lipids, high-sensitivity C-reactive protein (hs-CRP) and insulin resistance, homeostasis model assessment (HOMA-IR) were measured. The preparation of FA methyl esters and their gas chromatography (GC) analysis were also performed.Results: HbA1c, plasma insulin, HOMA-IR and triglycerides were higher in patients with T2DM, whereas HDL-C was lower in those subjects. Levels of pro-oxidative enzyme malondialdehyde (MDA) and hs-CRP were significantly higher, and anti-oxidative enzymes SOD and PON-1 activity were decreased in T2DM patients. N-6 PUFAs were higher in T2DM patients, particularly linoleic acid (LA, 18:2 n-6) and arachidonic acid (AA, 20:4 n-6), whereas n-3 PUFA, docosahexaenoic acid (DHA, 22:6 n-3) was lower in T2DM patients. Using regression analysis, we have shown that only LA and DHA independently predicted PON-1 activity of all participants, particularly in patients with T2DM.Conclusions: Decreased serum PON-1 activity may, in part, be influenced by higher levels of LA and lower levels of DHA in patients with T2DM. Prospective, randomized studies are necessary to confirm these preliminary findings.

1858 C/T Polymorphism of the Protein Tyrosine Phosphatase Nonreceptor 22 Gene and Rheumatoid Arthritis Risk in Europeans: A Meta-Analysis Based on 19 Case–Control Studies - Uncorrected Proof

Lu-ming Nong, Ke-wei Ren, Nan-wei Xu, Dong Zhou — 2012-01-03

Background and Aims: A single nucleotide polymorphism (SNP) of the protein tyrosine phosphatase nonreceptor gene (PTPN22) confers susceptibility to rheumatoid arthritis (RA) and certain other classical autoimmune diseases. The association between PTPN22 1858C/T polymorphism and the risk of RA is still controversial and ambiguous; therefore, we performed this meta-analysis to confirm some relationships.Methods: We conducted a search in the PubMed database without a language limitation, covering all papers published until June 20, 2011. Overall, 19 case-control studies with 11,727 cases and 12,640 controls were retrieved based on the search criteria for RA susceptibility related to the 1858C/T polymorphism. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of this association. Publication bias was assessed with Eggers test.Results: We found that PTPN22 1858C/T polymorphism could increase RA risk in overall genetic models in Europeans (T-allele vs. C-allele, OR = 1.54, 95% CI = 1.47–1.62, Pheterogeneity = 0.143; TT vs. CC, OR = 2.86, 95% CI = 2.29–3.57, Pheterogeneity = 0.302; TC vs. CC, OR = 1.45, 95% CI = 1.38–1.53, Pheterogeneity = 0.273; TT + TC vs. CC, OR = 1.49, 95% CI = 1.42–1.56, Pheterogeneity = 0.208; TT vs. TC + CC, OR = 2.52, 95% CI = 1.95–3.25, Pheterogeneity = 0.296). Furthermore, significant relationships were detected among PTPN22 1858C/T polymorphism and RF+ or RF− RA risk. No obvious evidence of publication bias was detected in the overall analysis.Conclusions: Our study indicated that PTPN22 1858T allele was significantly associated with increased RA risk.

Is the C677T Polymorphism in Methylenetetrahydrofolate Reductase Gene a Risk Factor for Diabetic Nephropathy or Diabetes Mellitus in a Chinese Population? - Uncorrected Proof

2012-01-03

Background and Aims: To date, case-control studies on the association between C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene and diabetes mellitus (DM) or diabetic nephropathy (DN) in different populations have provided inconclusive results. To clarify the effect of the C677T polymorphism on the risk of both DM and DN in a Chinese population, a meta-analysis was performed.Methods: A comprehensive literature search was conducted to collect data from all case-control observational studies that investigated association of C677T polymorphism in MTHFR gene with DM or DN in a Chinese population.Results: Overall, 12 studies in a Chinese population published up to 2011 were combined, and the heterogeneity among them varied from none to moderate. The 677T allele showed significant association with DN (OR = 1.97, 95% CI [1.71, 2.28], p <0.00001), but no relationship with DM (OR = 1.03, 95% CI [0.89, 1.18], p = 0.70) compared with the 677C allele in a Chinese population. Similarly, evidence of significant association with DN was detected in the additive model, the recessive model and the dominant model for allele T (additive model: OR = 3.26, 95% CI [2.46, 4.31], p <0.00001; recessive model: OR = 2.32, 95% CI [1.81, 2.97], p <0.00001; dominant model: OR = 2.35, 95% CI [1.89, 2.91], p <0.00001); however, no relationship with DM was found (additive model: OR = 1.01, 95% CI [0.76, 1.35], p = 0.94; recessive model: OR = 0.98, 95% CI [0.76, 1.26], p = 0.87; dominant model: OR = 1.23, 95% CI [0.91, 1.65], p = 0.18). There were no sources of bias in the selected studies, and the sensitivity analysis (exclusion of studies not in Hardy–Weinberg equilibrium) suggested stability of this meta-analysis.Conclusions: C677T polymorphism in MTHFR gene may be a risk factor for DN, but not for DM, in a Chinese population.

Effect of CYP1A1 MSPI Polymorphism on the Relationship Between TP53 Mutation and CDKN2A Hypermethylation in Chinese Patients with Non-small Cell Lung Cancer - Uncorrected Proof

2011-12-08

Background and Aims: The molecular mechanisms of lung cancer susceptibility have not been fully understood. Although it has been described that germline polymorphisms are associated with either mutation or methylation of genes, the link between gene polymorphisms and gene-gene interactions has not been investigated. Therefore, we conducted this study to determine whether CYP1A1/GSTM1 polymorphisms can affect the relationship between TP53 mutation and CDKN2A hypermethylation in lung cancer.Methods: This study included 196 primary non-small cell lung cancer (NSCLC) patients. CYP1A1 MSPI and GSTM1 polymorphisms were characterized through PCR-RFLP on DNA isolated from peripheral lymphocytes. TP53 mutations of exons 5 through 9 and CDKN2A promoter hypermethylation in both cancer tissues and corresponding normal tissues were analyzed by direct sequencing and methylation-specific PCR (MSP) respectively.Results: TP53 mutation in the tumor was associated with squamous cell histology and CDKN2A methylation was associated with older age (≥60 years), heavy smoking (>30 pack-years), squamous cell histology and advanced stage (stage II–IV). After adjusting for age, sex, smoking degree, histology type and TNM stage, the correlation between TP53 mutation and CDKN2A methylation was significant in patients with CYP1A1 risk genotype (p = 0.038), but not in those with CYP1A1 homogeneity wild genotype (p = 0.151).Conclusions: This may suggest that TP53 mutation and CDKN2A methylation specifically interact to promote lung tumorigenesis in subjects with CYP1A1 risk genotype but not in those with CYP1A1 wild-type homozygotes, implying different pathways for the development of lung carcinoma with respect to CYP1A1 polymorphism.

Umbilical Cord Blood: Lessons Learned and Lingering Challenges After More Than 20 Years of Basic and Clinical Research - Uncorrected Proof

Hector Mayani — 2011-12-08

Abstract: During the last 23 years, cord blood research has played important roles both in experimental and clinical hematology. Cord blood-derived hematopoietic stem and progenitor cells have been shown to possess particular biological features and their study has been very important in our understanding of hematopoietic development. Today, >20,000 umbilical cord blood (UCB) transplants have been performed worldwide and ∼460,000 UCB units are being stored in >47 UCB banks worldwide. Here a brief overview on some of the most relevant issues regarding cord blood research is presented.

Reply: Association Between MMP2-1306C/T Polymorphism and Digestive Cancer Risk: Need for Clarification of Data in the Recent Meta-analysis - Uncorrected Proof

Le-Yao Zhang, Ke-Wei Ren — 2011-12-07

Thank you very much for sharing the Letter to the Editor. After reviewing the authors’ comments and carefully checking the original studies and raw data, we are pleased to reply and to clarify their questions, one by one, related to our paper published in Archives of Medical Research .

Association Between MMP2-1306C/T Polymorphism and Digestive Cancer Risk: Need for Clarification of Data in a Recent Meta-analysis - Uncorrected Proof

Feng Pan, Jing Tian, Ying Zhang, Yue-Yin Pan — 2011-12-07

We read with great interest the recent article entitled Meta-Analysis of MMP2 -1306T Allele as a Protective Factor in Digestive Cancer by Zhang et al. . The meta-analysis by Zhang et al. included 10 case-control studies involving 2,380 cases and 4,574 controls to investigate the association between matrix metalloproteinase-2 (MMP-2)-1306C/T gene polymorphism and digestive cancer susceptibility, and the results suggested that MMP-2-1306T allele might act as a protective factor for the development of digestive cancer as well as a low-penetrance susceptibility digestive cancer biomarker. It is an interesting study. Nevertheless, we would like to raise several concerns related to this article.

Association Between Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR) C677T and Risk of Myocardial Infarction: A Meta-analysis for 8,140 Cases and 10,522 Controls - Uncorrected Proof

Chao Xuan, Xiao-yan Bai, Ge Gao, Qin Yang, Guo-wei He — 2011-12-07

Background and Aims: The methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism has been reported to be associated with myocardial infarction (MI), but results from previous studies are conflicting. The present study aimed at investigating the association between this polymorphism and risk of MI using a meta-analysis on the published studies.Methods: Medline, EBSCO, BIOSIS, and Cochrane Library were searched to identify eligible studies published in English before August, 2011. Data were extracted using standardized methods. The association was assessed by odds ratio (OR) with 95% confidence intervals (CI). Begg’s test was used to measure publication bias.Results: A total of 30 case-control studies containing 8,140 MI cases and 10,522 controls were involved in this meta-analysis. Overall, significant association was found between MTHFR C677T polymorphism and risk of MI when all studies pooled with fixed-effects model for TT vs. CT (OR = 1.183, 95% CI: 1.076–1.300). In the subgroup analysis, the same association was found in overall Caucasians (OR = 1.139, 95% CI: 1.007–1.288) and young/middle-aged (<50 years) Caucasians (OR = 1.275, 95% CI: 1.077–1.509). No associations were detected between MTHFR C677T and the risk of MI in elderly male or female Caucasians, East Asians, South Asians, and African-Americans.Conclusions: Meta-analysis results suggest that the MTHFR C677T polymorphism was associated with risk of MI in young/middle-aged Caucasians. The effect of the variants on the expression levels and the possible functional role of the variants in MI should be addressed in further studies.