An updated meta-analysis of transforming growth factor-β1 gene: Three well-characterized polymorphisms with asthma

The association between TGF-β1 polymorphisms and asthma risk has been widely reported, but results were controversial. We performed this meta-analysis based on the Preferred Reporting Items for Systematic Reviews and meta-analyses statement (PRISMA). Electronic database of Pub Med, Web of Science, CBM, and CNKI were searched for eligible articles published up to September, 2013. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Finally, a total of 20 articles were identified, 17 studies with 3694 cases and 5613 controls for C-509T polymorphism, 7 studies with 1109 cases and 1098 controls for T869C polymorphism and 5 studies with 849 cases and 829 controls for G915C polymorphism. For C-509T, significant associations with asthma were found in Asians (TT + TC vs. CC: P = 0.004, OR = 1.43, 95%CI = 1.12–1.81, P_{heterogeneity} = 0.001) and in Caucasians (P = 0.05, OR = 1.16, 95%CI = 1.00–1.34, P_{heterogeneity} = 0.36). With respect to T869C, a small significant association was observed in overall analysis of allele contrasts(C vs. T: OR = 1.14, 95%CI: 1.01–1.29, P = 0.03) and homozygote comparison (CC vs. TT: OR = 1.29, 95%CI: 1.00–1.65, P = 0.05), but no significant risks were found among Caucasian population and Asian population. For G915C polymorphism, no significant association with asthma risk was demonstrated in overall analysis and subgroup analyses according to ethnicity for all genetic models. This meta-analysis suggested that TGF-β1 C-509T and T869C polymorphisms may be risk factors for asthma.     

Association of PTPN22 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population

Lymphoid protein tyrosine phosphatase encoded by protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays an important regulatory role in T- and B-cell activation. This study investigated PTPN22 −1123G/C and intron 16 T/C polymorphisms in 372 patients with chronic hepatitis B virus (HBV) infection, 72 HBV infection resolvers and 273 healthy controls. Genotypic association tests between groups assuming codominant, dominant or log-additive genetic models were performed. In recessive model, PTPN22 −1123G/C genotype GG in healthy controls was more frequent than infection resolvers (P = 0.037, OR = 3.606, 95%CI = 1.079–12.053) and this genotype in HBV patients was more frequent than resolvers although the difference was not significant (P = 0.059). The PTPN22 intron 16 T/C genotype TC in cirrhosis patients was significantly higher than asymptomatic carriers (ASC) in codominant (P = 0.028, OR = 9.792, 95%CI = 1.281–74.832) and overdominant (P = 0.025, OR = 10.142, 95%CI = 1.332–77.214) models. This genotype in hepatocellular carcinoma (HCC) patients was significantly higher than ASC in codominant (P = 0.034, OR = 9.200, 95%CI = 1.176–71.990) and overdominant (P = 0.030, OR = 9.677, 95%CI = 1.241–75.442) models. These findings suggest that PTPN22 polymorphisms may predispose the chronicity or the development of cirrhosis and HCC in HBV infection.     

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility

BackgroundMicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach.MethodsA PubMed database search was conducted during August 2013 to identify case–control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software.ResultsOur meta-analysis of six case–control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI = 0.642–1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR = 0.911, 95% CI = 0.710–1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR = 0.616, 95% CI = 0.384–0.981, (T vs. C allele) and OR = 0.386, 95% CI = 0.226–0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR = 1.263, 95% CI = 1.136–1.405, G vs. A allele).ConclusionsThe present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.     

A dual role for Mannan-binding lectin-associated serine protease 2 (MASP-2) in HIV infection

BackgroundMannan-binding lectin (MBL) – associated serine protease 2 (MASP-2) co-activates the lectin pathway of complement in response to several viral infections. The quality of this response partly depends on MASP2 gene polymorphisms, which modulate MASP-2 function and serum levels. In this study we investigated a possible role of MASP2 polymorphisms, MASP-2 serum levels and MBL-mediated complement activation in the susceptibility to HIV/AIDS and HBV/HCV coinfection.MethodsA total of 178 HIV patients, 89 (50%) coinfected with HBV/HCV, 51.7% female, average age 40 (12–73) years, and 385 controls were evaluated. MASP-2 levels and MBL-driven complement activation were evaluated by enzyme-linked immunosorbent assay and 11 MASP2 polymorphisms from the promoter to the last exon were haplotyped using multiplex sequence-specific PCR.ResultsGenotype distribution was in Hardy-Weinberg equilibrium and differed between HIV+ patients and controls (P = 0.030), irrespective of HBV or HCV coinfection. The p.126L variant, which was associated with MASP-2 levels <200 ng/mL (OR = 5.0 [95%CI = 1.3–19.2] P = 0.019), increased the susceptibility to HIV infection (OR = 5.67 [95%CI = 1.75–18.33], P = 0.004) and to HIV + HBV+ status (OR = 6.44 [95%CI = 1.69–24.53, P = 0.006). A similar association occurred with the ancient haplotype harboring this variant, AGCDV (OR = 2.35 [95%CI = 1.31–4.23], P = 0.004). On the other hand, p.126L in addition to other variants associated with low MASP-2 levels—p.120G, p.377A and p.439H, presented a protective effect against AIDS (OR = 0.25 [95%CI = 0.08–0.80], P = 0.020), independently of age, sex, hepatic function and viral load. MASP-2 serum levels were lower in HIV+ and HIV + HBV+ patients than in controls (P = 0.0004). Among patients, MASP-2 levels were higher in patients with opportunistic diseases (P = 0.001) and AIDS (P = 0.004). MASP-2 levels correlated positively with MBL/MASP2-mediated C4 deposition (r = 0.29, P = 0.0002) and negatively with CD4+ cell counts (r = −0.21, P = 0.018), being related to decreased CD4+ cell counts (OR = 5.8 [95%CI = 1.23–27.5, P = 0.026).ConclusionsGenetically determined MASP-2 levels seem to have a two-edge effect in HIV and probably HCV/HBV coinfection, whereas low levels increase the susceptibility to infection, but on the other side protects against AIDS.     

Meta-analysis of the methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to Alzheimer's disease

No clear consensus has been reached at the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and Alzheimer's disease (AD) risk. Thus in this meta-analysis, a total of 19 case–control studies was assessed to evaluate the possible association. The data demonstrated that the frequency of T677 allele (T vs. C) was significantly associated with susceptibility to AD in all subjects (OR = 1.15, 95% CI = 1.06–1.26) and in East Asians (OR = 1.22, 95% CI = 1.08–1.39). There was statistical difference between AD patients and the controls under recessive genetic mode (CT + TT vs. CC) and homozygote comparison (TT vs. CC) in all subjects and in East Asians as well. Despite a small effect of the polymorphism on late-onset AD (LOAD) risk, MTHFR C677T polymorphism was not a major risk factor for LOAD in East Asians and Caucasians. A subgroup analysis in the subjects without APOE ?4 alleles showed T677 allele significantly increased risk of AD in all subjects (OR = 1.21, 95% CI: 1.04–1.42) and in East Asians (OR = 1.28, 95% CI: 1.06–1.55). However, no association was found in Caucasians. In conclusion, this meta-analysis supports that MTHFR C677T polymorphism is capable of causing AD susceptibility in East Asians, not in Caucasians.     

A meta-analysis of P2X7 gene-1513A/C polymorphism and pulmonary tuberculosis susceptibility

ObjectiveA meta-analysis was performed to determine the association between P2X7-1513A/C polymorphism and pulmonary tuberculosis susceptibility.MethodsBased on comprehensive searches of the MEDLINE, EMBASE and ISI Web of knowledge, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between P2X7-1513A/C polymorphism and pulmonary tuberculosis susceptibility.ResultsA total of 1916 cases and 2194 controls in 10 studies were pooled together for evaluation of the overall association between P2X7-1513A/C polymorphism and susceptibility of pulmonary tuberculosis. Allele model (A vs. C: p = 0.15; OR = 0.86, 95% CI = 0.69–1.06), homozygous model (AA vs. CC: p = 0.22; OR = 0.78, 95% CI = 0.53–1.16), and heterozygous model (AC vs. CC: p = 0.23; OR = 0.80, 95% CI = 0.56–1.15) did not show decreased risk of developing pulmonary tuberculosis. Similarly, dominant model (AA + AC vs. CC: p = 0.19; OR = 0.80, 95% CI = 0.56–1.12) and recessive model (AA vs. AC + CC: p = 0.21; OR = 0.85, 95% CI = 0.66–1.10) failed to show decreased risk of developing pulmonary tuberculosis. In Indians, allele model (A vs. C: p = 0.0006; OR = 0.69, 95% CI = 0.55–0.85), and recessive model (AA vs. AC + CC: p = 0.0003; OR = 0.62, 95% CI = 0.48–0.80) indicated significant association between P2X7-1513A/C polymorphism and susceptibility to pulmonary tuberculosis.ConclusionsOur pooled data suggest a association between P2X7-1513A/C polymorphism and the prevalence of pulmonary tuberculosis among Indian populations.     

Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: A meta-analysis

ObjectiveMany studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality.MethodsRelevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality.ResultsSignificant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR = 0.75, 95% CI = 0.59–0.94) and severe sepsis subgroup for LL + L2 versus 22 (OR = 0.67, 95% CI = 0.47–0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models.ConclusionsAccording to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality.     

Examiner characteristics and interrater reliability in a communication OSCE

ObjectiveTo identify inter-individual examiner factors associated with interrater reliability in a summative communication OSCE in the 4th study year.MethodsThe OSCE consists of 4 stations assessed with a 4-item 5-point global rating instrument. A bivariate secondary analysis of interrater reliability in relation to 4 examiner factors (gender, profession, OSCE experience, examiner training) was conducted. Intraclass correlation coefficients (ICC) were calculated and compared between examiner dyads of different similarity.Results169 pairwise ratings from 19 different examiners in 16 dyads were analysed. Interrater reliability is significantly higher in examiner dyads of same vs. different gender (ICC = 0.76 (95%CI = 0.65-0.83) vs. ICC = 0.41 (95%CI = 0.21-0.57)), in dyads of two clinicians vs. non-clinical/mixed professions (ICC = 0.72 (95%CI = 0.56-0.83) vs. ICC = 0.57 (95%CI = 0.41-0.69)), and in dyads with high vs. low/mixed OSCE experience (ICC = 0.73 (95%CI 0.50-0.87) vs. ICC = 0.56 (95%CI = 0.41-0.69)). Participation in recent examiner training had no influence on ICCs.ConclusionBetter concordance of ratings between clinically active examiners might be a hint for context specificity of good communication. Higher interrater reliability between examiners with same gender may indicate gender-specific communication concepts.Practice implicationsMedical faculties introducing summative assessment of communication competence should focus the influence of examiner characteristics on interrater reliability.     

Interleukin-18 promoter -607 C/A and -137 G/C polymorphisms and susceptibility to type 1 diabetes: A meta-analysis

ObjectiveThe aim of this study was to determine whether the functional interleukin-18 (IL-18) promoter -607 C/A (rs1946518) and -137 G/C (rs187238) polymorphisms are associated with susceptibility to type 1 diabetes (TID).MethodsA meta-analysis was conducted to assess the associations between the IL-18 -607 C/A and -137 G/C polymorphisms and T1D in overall and by ethnic group.ResultsA total of 6075 cases and 5744 controls from ten studies were considered in this meta-analysis. In all study subjects, the meta-analysis showed no association between T1D and the IL-18 -607 C allele (OR = 1.083, 95% CI = 0.930–1.260, p = 0.307). However, stratification by ethnicity indicated an association between the IL-18 -607 C allele and T1D in Asians (OR = 1.506, 95% CI = 1.172–1.936, p = 0.001), but not in Europeans (OR = 0.988, 95% CI = 0.808–1.209, p = 0.907). Analysis using recessive and dominant models and homozygote contrast showed the same -607 C allele pattern in Asians and Europeans. Meta-analysis of the IL-18 -137 G/C polymorphism showed no association between T1D and the IL-18 -137 G allele in all study subjects (OR = 1.066, 95% CI = 0.926–1.2289, p = 0.375). Stratification by ethnicity indicated no association between the IL-18 -137 G allele and T1D in Europeans and Asians (OR = 1.021, 95% CI = 0.961–1.085, p = 0.504; OR = 0.851, 95% CI = 0.5821–1.245, p = 0.406).ConclusionsOur meta-analysis demonstrates that the IL-18 -607 C/A polymorphism may be associated with susceptibility to T1D in Asians, but not in Europeans.     

Correlation between viral load,multiplicity of infection,and persistence of HPV16 and HPV18 infection in a Dutch cohort of young women

BackgroundPersistent high-risk human papillomavirus infection precedes the development of cervical cancer. Here we evaluated the contribution of HPV16/18 viral load and the presence of infections with multiple HPV types to persistence and clearance of HPV16/18 infections.MethodsVaginal self-swabs were obtained from young women (16–29 y) with one year interval. HPV genotyping was performed using the highly sensitive SPF10-DEIA-LiPA₂₅ system. HPV16/18 DNA loads were quantified via an adapted, highly sensitive qPCR protocol targeting the L1 gene.ResultsWe identified 227 HPV16 and 111 HPV18 infections with follow-up. For HPV16 132/227 (58%) were persistent and 95/227 cleared. For HPV18 49/111 (44%) infections were persistent and 62/111 cleared. Baseline viral load was significantly higher in persistent infections than in clearing infections for both HPV16 (p = 0.022) and HPV18 (p = 0.013). At baseline, only HPV16 viral load was significantly higher in multiple HPV infections compared with single infections (p = 0.003). In logistic regression analysis HPV16 and HPV18 viral load were found to contribute to persistency with OR = 1.279 (95%CI = 1.074–1.524) and OR = 1.256 (95%CI = 1.028–1.533) per log-unit increase HPV16 and HPV18 viral load respectively. The presence of multiple HPV type infections was not associated with higher persistency.ConclusionHPV16/18 viral load might be used as a marker for persisting infections and is affected by the presence of multiple HPV infections. Evaluation of these parameters at the population level may be of value to assess the presence of persistent or clearing HPV16/18 infections as an early marker, and may provide useful quantitative information in (epidemiological) vaccine monitoring studies.     

Risk factors for cytomegalovirus DNAemia following haploidentical stem cell transplantation and its association with host hepatitis B virus serostatus

BackgroundThe risk factors associated with CMV DNAemia are not well known after haploidentical stem cell transplantation (SCT).ObjectivesThis study investigated the risk factors and prognosis for CMV DNAemia among CMV seromatched donors and recipients (D+/R+).Study designA retrospective study of patients undergoing haploidentical stem cell transplantation (SCT) between January 2010 and January 2012 was conducted. Cox regression analysis was performed to identify the risk factors for CMV DNAemia. These possible factors included recipient/donor age, recipient/donor gender, gender disparity, recipient HBsAg serostatus, diagnosis, risk stratification, anti-thymocyte globulin (ATG) dose (6 mg/kg,10 mg/kg), early neutrophil engraftment (≤12 days, >12 days), absolute lymphocyte count on day 30 (ALC30) and the occurrence of acute GVHD before CMV DNAemia.ResultsThe total number of patients was 248 with median age of 31 years (range, 14–56). The cumulative incidence of CMV DNAemia (146/248) was 59.5%. CMV DNAemia was first detected after a median of +35 days (range,12–82). Seventeen patients (17/146, 11.6%) developed CMV disease. Multivariate analysis identified HBsAg seropositivity (P = 0.002, hazard ratio (HR) = 1.833; 95%CI = 1.257–2.673) and the occurrence of acute GVHD before CMV DNAemia (P = 0.014; HR = 1.520; 95%CI = 1.088–2.124) as risk factors for CMV DNAemia. CMV DNAemia was associated with subsequent II-IV acute graft-versus-host disease (GVHD) (P = 0.014), III-IV aGVHD (P = 0.013) and chronic GVHD (P = 0.008). Totally, CMV DNAemia was found to be a poor prognostic factor in terms of non-relapse mortality (NRM) (P = 0.003, HR = 2.730; 95%CI = 1.406–5.197), and overall survival (OS) (P = 0.045, HR = 1.654; 95%CI = 1.012–2.701).ConclusionsOur data showed HBsAg seropositivity was associated with an increased risk of cytomegalovirus DNAemia. Detection of CMV DNAemia proved to be a poor prognostic factor for haploidentical patients.     

Association between IFNL4 rs368234815 polymorphism and sustained virological response in chronic hepatitis C patients undergoing PEGylated interferon/ribavirin therapy: A meta-analysis

Background and aimsMany studies have been published on the association between IFNL4 rs368234815 single-nucleotide polymorphism (SNP) and sustained virological response (SVR) in chronic hepatitis C (CHC) patients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV). Because of the variable and sometimes inconsistent results, we performed a meta-analysis to estimate the association between these factors.MethodsWe conducted a search of the literature published prior to July 1, 2014. The pooled results were analyzed as the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effect model.ResultsThe pooled results revealed that the rs368234815 TT/TT genotype was significantly correlated with SVR in HCV-1/4-infected Caucasian patients (OR = 4.65, 95% CI = 3.36–6.42, P < 0.00001) but not in HCV-2/3-infected Caucasian patients (OR = 1.44, 95% CI: 0.89–2.33, P = 0.13). Conversely, the rs368234815 ΔG/ΔG genotype was significantly linked to treatment failure in Caucasian patients (OR = 0.49, 95% CI: 0.38–0.64, P < 0.00001), regardless of the HCV genotype.ConclusionThe results of the meta-analysis suggest that IFNL4 rs368234815 polymorphism may be a predictor of SVR in Caucasian HCV-1/4-infected patients.     

Association of IL-17A and IL-17F polymorphisms with gastric cancer risk in Asians: A meta-analysis

Increasing number of studies focused on the association of IL-17A rs2275913 and IL-17F rs763780 polymorphisms with gastric cancer (GC) risk. However, the results were inconsistent. To elucidate the exact association, we performed the present meta-analysis. Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched for potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to evaluate the strength of association. Eight studies for IL-17A rs2275913 (3345 cases and 4427 controls) and five studies for IL-17F rs763780 (1784 cases and 2592 controls) were finally included. The results indicated that individuals with AA genotype of IL-17A rs2275913 polymorphism were associated with increased GC risk compared with wild-type GG (OR = 1.61, 95% CI = 1.17–2.23, P = 0.004); A allele was significantly associated with increased GC risk compared with G allele (OR = 1.22, 95% CI = 1.06–1.41, P = 0.007). IL-17F rs763780 polymorphism was also significantly associated with increased GC risk (CC vs. CT: OR = 1.40, 95% CI = 1.04–1.88, P = 0.025; CT vs. TT: OR = 1.35, 95% CI = 1.16–1.58, P < 0.001; C allele vs. T allele: OR = 1.30, 95% CI = 1.15–1.47, P < 0.001). In summary, IL-17A rs2275913 A/G polymorphism and IL-17F rs763780 C/T polymorphism might be associated with increased GC risk in Asians. Further large-scale studies are still required to confirm the results of this meta-analysis.     

A meta-analysis of the relationship between MYO9B gene polymorphisms and susceptibility to Crohn’s disease and ulcerative colitis

ObjectiveBoth Crohn’s disease (CD) and ulcerative colitis (UC) have a complex etiology involving multiple genetic and environmental factors. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. The aim of this meta-analysis was to clarify the impact of MYO9B gene polymorphisms on CD and UC risk.MethodsThe PubMed, Elsevier Science Direct and Embase databases were searched to identify eligible studies that were published before October 2014. Data were extracted and pooled crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsA total of 11 studies, containing 3297 CD cases, 3903 UC cases and 8174 controls were included in this meta-analysis. Bonferroni correction results showed that rs1545620 A/C polymorphism of MYO9B gene was associated with both CD and UC susceptibility in Caucasians (OR = 0.88, 95% CI = 0.82 ∼ 0.95, P = 0.001; OR = 0.82, 95% CI = 0.76 ∼ 0.89, P < 0.001), but not in Chinese. rs1457092 G/T and rs2305764 C/T polymorphisms are associated with UC susceptibility (OR = 0.85, 95% CI = 0.79 ∼ 0.91, P < 0.001; OR = 0.88, 95% CI = 0.83 ∼ 0.93, P < 0.001), but not with CD susceptibility in Caucasians.ConclusionsThis meta-analysis suggested that rs1545620 is both CD and UC susceptible locus in Caucasians; rs1457092 and rs2305764 are UC susceptible loci, but are not CD susceptible loci in Caucasians. Further studies with more sample size are needed for a definitive conclusion.     

Genetic polymorphisms of interleukin-6 gene and susceptibility to coronary artery disease in Chinese population: Evidence based on 4582 subjects

The aim of this study was to explore whether interleukin-6 (IL-6) gene (−174 G/C and −572 C/G) polymorphisms are associated with susceptibility to coronary artery disease (CAD) risk in Chinese population. All the statistical tests were performed using Stata version 11.0. Twelve articles involving 16 studies were included in this meta-analysis, covering a total of 2309 CAD cases and 2273 controls. For IL-6 gene −572 C/G polymorphism, the results showed evidence for significant association between IL-6 gene −572 C/G polymorphism and CAD risk (for G allele vs. C allele: OR = 1.48, 95% CI = 1.26–1.74, p < 0.001; for G/G vs. C/C: OR = 2.60, 95% CI = 1.54–4.39, p < 0.001; for G/G vs. G/C + C/C: OR = 2.15, 95% CI = 1.35–3.42, p = 0.001; for G/G + G/C vs. C/C: OR = 1.55, 95% CI = 1.29–1.85, p < 0.001). However, for IL-6 gene −174 G/C polymorphism, no significant association was found between this variation and CAD risk. In summary, our meta-analysis showed evidence that IL-6 gene −572 C/G polymorphism may be a risk factor for CAD susceptibility. For IL-6 gene −174 G/C polymorphism, no significant association was found between this variation and CAD risk.     

Emergent US adenovirus 3 strains associated with an epidemic and serious disease

BackgroundAdenovirus type 3 (HAdV3) is one of the most prevalent serotypes detected globally. Variants of HAdV3 have been associated with outbreaks of severe disease.ObjectivesTo better understand genetic diversity of circulating HAdV3s and examine risk factors for severe disease.Study designRestriction enzyme analysis for genomic characterization of clinical HAdV3 isolates detected by 15 collaborative US laboratories during the period July 2004 to May 2007. Multivariate modeling was employed for statistical analyses.ResultsThe most common HAdV3 types of 516 isolates studied were HAdV3a2 (36.9%), HAdV3a50 (27.1%), HAdV3a51 (18.0%), and HAdV3a17 (4.6%). Non-HAdV3a genome types were rare (1.2%). HAdV3a50 and HAdV3a51 are newly described variants which became more prevalent in 2006 and 2007 and have been associated with at least one epidemic. Their uniqueness was determined by specific banding profiles generated by digests with endonucleases BclI, BglII, and HindIII. Multivariable risk factor modeling demonstrated that children under 2 years of age (OR = 2.7; 95%CI 1.6–4.6), persons with chronic disease (OR = 5.1; 95%CI 2.6–9.8), persons infected with HAdV3a2 (OR = 3.0; 95%CI 1.5–6.0), with HAdV3a50 (OR = 2.5; 95%CI 1.2–5.2), or with multiple or rare strains (OR = 2.8; 95%CI 1.3–6.5) were at increased risk of severe HAdV3 clinical disease.ConclusionsIn the study period considerable genetic diversity was found among US clinical HAdV3 strains. Novel variants emerged and became prevalent. One such emergent strain may be associated with more severe clinical disease.     

FCRL3 gene polymorphisms as risk factors for rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. As a member of FCRLs clusters, Fc receptor-like 3 (FCRL3) has been recognized as a neoteric autoimmune activation factor for RA. The aim of our study is to evaluate the correlation between four single-nucleotide polymorphisms (SNPs) on FCRL3 and RA risk in a Chinese Han population.Material and methodsThe hospital-based case-control study included 630 RA patients together with 696 healthy individuals as the control group and all subjects are Chinese ancestry. Four tagging single-nucleotide polymorphisms (tag-SNPs) on FCRL3 were selected and genotyped by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to evaluate the correlations between FCRL3 polymorphisms and RA. A systematic meta-analysis was also carried out based on the present study and previously published studies to further examine the association between FCRL3 variations and RA risk.ResultsSignificant association was found between −169T/C SNP and RA risk (CC vs. TT, OR = 1.62, 95% CI = 1.18–2.22; TC/CC vs. TT, OR = 1.47, 95% CI = 1.18–1.84; C vs. T, OR = 1.32, 95% CI = 1.12–1.54). Apart from that, mutations of −169T/C was significantly correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positive status. The meta-analysis also suggested that −169T/C mutation might have positive correlation with risk of RA in the overall population, particularly for Asian. Stratified analysis based on clinical characteristics of RF and ACPA also provided evidence that −169T/C polymorphisms could alter phenotypes of RA.ConclusionThe FCRL3 −169T/C variant was significantly linked with an increased RA risk in the Chinese Han population. Moreover, this meta-analysis also provides notion that −169T/C variant could act as a susceptible factor for RA. However, further investigations about the functional impacts of this polymorphism are essential to confirm the above conclusions.     

Relationship between depression and frailty in older adults: A systematic review and meta-analysis

AimDepression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta- analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty.MethodsTwo authors searched major electronic databases from inception until November-2016 for cross-sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders.ResultsFrom 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07–47.10, I² = 94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66–7.35, k = 11), also after adjusting for potential confounders (OR = 2.64; 95%CI: 1.59–4.37, I² = 55%, k = 4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00–55.30, I² = 97%). People with depression were at increased odds of having frailty (OR = 4.07, 95%CI 1.93–8.55, k = 8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95–7.08, I² = 98%, k = 4), whilst in two studies frailty increased the risk of incident depression with an OR = 1.90 (95%CI 1.55–2.32, I² = 0%).ConclusionThis meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted.     

The T &gt; A (rs11646213) gene polymorphism of cadherin-13 (CDH13) gene is associated with decreased risk of developing hypertension in Mexican population

Hypertension is a major public health problem affecting about 30% of the adult population and is associated with an increased risk of developing metabolic and cardiovascular disease. Recent reports have shown that the T-cadherin receptor characteristically expressed on endothelial and vascular smooth muscle cells is involved in hypertension. The aim of the present study was to evaluate the role of cadherin-13 (CDH13) gene polymorphisms as susceptibility markers for hypertension in Mexican population. Six CDH13 polymorphisms (rs11646213, rs11646411, rs6563943, rs3096277, rs3784990 and rs254340) were genotyped by 5′ exonuclease TaqMan assays in a group of 644 hypertensive and 765 non-hypertensive individuals. Under co-dominant, recessive, and additive models, the CDH13 T > A (rs11646213) polymorphism was associated with decreased risk of developing hypertension when compared to non-hypertensive individuals (OR = 0.61, 95% CI: 0.42–0.89, P_co-dom = 0.019; OR = 0.63, 95% CI: 0.46–0.87, P_res = 0.005; OR = 0.80, 95% CI: 0.66–0.96, P_add = 0.016, respectively). All models were adjusted by gender, age, body index mass, type II diabetes mellitus, alcohol consumption, dyslipidemia and smoking habit. Linkage disequilibrium analysis showed one haplotype (TCACGG) with decreased frequency in hypertensive when compared to non-hypertensive individuals (OR = 0.52, 95% CI: 0.33–0.82, P = 0.0053). In summary, our data suggests that the CDH13 T > A (rs11646213) polymorphism is associated with decreased risk of developing hypertension in the Mexican population. In addition, it was possible to distinguish one haplotype associated with decreased risk and two for increased risk of develop hypertension.     

The MHC2TA 1614 C&gt;G gene polymorphism is associated with risk of developing acute coronary syndrome

BackgroundInflammation plays an essential role in the development and progression of atherosclerotic lesions. The major histocompatibility complex class II trans-activator (MHC2TA) is considered an important molecule in the inflammatory process regulation. The aim of the present study was to evaluate the role of MHC2TA gene polymorphisms as susceptibility markers for acute coronary syndrome (ACS).MethodsThree polymorphisms (−168 A>G, 1614 C>G, and 2536 G>A) of the MHC2TA gene were analyzed by 5′ exonuclease TaqMan genotyping assays in a group of 297 patients with ACS and 283 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis.ResultsThe 1614 C allele and CC genotype were associated with risk of developing ACS (PC = 0.014, OR = 1.37 and PC = 0.006, OR = 1.90, respectively). Based on Hosmer–Lemeshow Goodness of Fit test, the recessive model was selected to estimate risk between ACS patients and controls adjusted by cardiovascular risk factors using a multiple logistic analysis. In this case, the OR adjusted was 1.78 for the 1614 CC genotype (P = 0.023). The analysis of linkage disequilibrium showed one risk haplotype (ACG) and one protective haplotype (AGG) for developing ACS (P = 0.02, OR = 1.5 and P = 0.04, OR = 0.72, respectively).ConclusionThe results suggest that MHC2TA 1614 gene polymorphism could be involved in the risk of developing ACS.