Pacemaker Failure Due to Loss of Fluid Seal in a Patient with a 5/6 mm Pacemaker Header Port and a 5 mm Unipolar Lead

IntroductionBefore IS-1 (3.2 mm) standardization of pacemaker leads and connectors, 5/6 mm connector ports accomodated 5 mm or 6 mm diameter lead connector pins.Case reportA patient with sick sinus syndrome underwent implantation of a 5 mm unipolar atrial lead, mated to a 5/6 mm connector port Medtronic Spectrax Sx 5985 pacemaker. Pulse generator reached ERI in 2006, with change out to a Medtronic Sigma SSR306 (5/6 mm connector port) and preservation of the 5 mm lead. She was admitted in 2010 for atrial lead non capture from blood leak and corrosion of the header-connector pin apparatus.Discussion5/6 mm pacemaker header ports have a 5 mm flexible sealing ring at the port entrance to seal 5 mm or 6 mm lead connector pins. The inner barrel diameter of the connector port is 6 mm and insertion of a 5 mm lead results in a 0.5 mm tolerance circumferentially. Should the seal be compromised, blood can corrode the apparatus. To minimize this, we can employ (a) a cinching tie to further seal the silicone ring (b) universal adaptor sleeves (c) splice kits (d) lead adaptor kits. Aging leads, adaptor kits or sleeves themselves can result in lead failure. It may be safer to re-implant the entire system.ConclusionA 5/6 mm configuration pacemaker header connector port allows for significant tolerances when a 5 mm lead is used. Consideration must be made to prevent leaks.     

An updated meta-analysis on the association of TGF-β1 gene promoter -509C/T polymorphism with colorectal cancer risk

AimPublished data on the association between transforming growth factor-β1 (TGF-β1) gene promoter-509C/T polymorphism and colorectal cancer (CRC) risk are inconsistent and inconclusive. To derive a more precise estimation of this association, a meta-analysis was carried out.MethodsMeta-analysis was performed to evaluate reported studies of the relationship between TGF-β1 gene promoter-509C/T polymorphism and colorectal cancer risk using fixed-effects model and random-effects model.ResultsWe observed an increased colorectal cancer risk among subjects carrying TGF-β1 gene promoter-509CC + CT genotype (odds ratio (OR) = 1.18%, 95% confidence interval (95% CI): 1.06–1.32) using 4440/6785 cases/controls in total population. We observed an increased risk of the TGF-β1 gene promoter -509CC, CT and CC + CT polymorphisms for colorectal cancer in population-based study (OR = 1.36, 95% CI: 1.19–1.56, OR = 1.18, 95% CI: 1.03–1.34 and OR = 1.26, 95% CI: 1.12–1.43, respectively) in stratified analysis. We observed an increased colorectal risk among CC and CC + CT carriers in European and American population (OR = 1.22, 95% CI: 1.04–1.43 and OR = 1.18, 95% CI: 1.02–1.38, respectively). We also observed an increased risk of colon cancer among subjects carrying CC + CT genotype (OR = 1.31, 95% CI: 1.05–1.63).ConclusionsThe present meta-analysis results suggest that TGF-β1 gene promoter -509C allele variant is a possible risk factor for developing colorectal cancer. Recommendations for further studies include pooling of individual data to verify results from the study and to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.     

Safety of Prunus africana and Warburgia ugandensis in asthma treatment

The aim of the study was to determine the possible cytotoxicity of the aqueous stem bark extracts of Prunus africana and Warburgia ugandensis to Vero E6 cells and acute toxicity in BALB/c mice. Despite being some of the most popular medicinal plants used in Africa, little is known about the safety. In-vitro cytotoxicity tests on Vero E6 cells were investigated using MTT assay to assess the safety of the two plant extracts. Vero E6 cells on growing to confluence were incubated with different drug concentrations for 48 h for the drug to take effect. Viability of the cells was measured by a scanning multiwell spectrophotometer, color intensity being equivalent to viable cells which reduce MTT to soluble formazan crystals. This was done by determining the CC₅₀ of the extracts, CC₅₀ being the concentration of the dose of the compound/extract that kills 50% of the cells. In acute toxicity a total of 55 mice were used. Mice were divided into eleven groups of 5 mice, one group served as negative control and ten groups received oral gavage doses at 500, 889.56, 1581.6, 2812.15 or 5000 mg/kg body weight once. Mortality and other signs of toxicity were recorded within 24 h and the weights of the surviving mice taken for 14 days thereafter. P. africana had CC₅₀ of 104.08 μg/ml while W. ugandensis had CC₅₀ > 250 μg/ml and both were classified as not cytotoxic. There was no mortality observed in groups of mice that received P. africana extracts at 500 and 889.56 mg/kg body weight. There was 20%, 60% and 100% mortality observed within 24 h for mice that received P. africana extracts at 1581.64, 2812.15 and 5000 mg/kg body weight respectively. Lethal dose (LD₅₀) for P. africana was 2201.207 mg/kg body weight. W. ugandensis extracts had no mortality recorded in all dose levels and the LD₅₀ was > 5000 mg/kg body weight. The weights of mice that survived the entire 14 days in all groups increased and were not significantly different from that of controls p > 0.05. From the in vitro and in vivo studies, the two extracts were safe to use. Though with their customary value among many Kenyan communities in management of asthma among other ailments there is a need for further validation of any anti-asthmatic properties and responsible chemical compounds to augment the findings.     

Discovery,characterization and comparison of inhibitors of Bacillus anthracis and Staphylococcus aureus replicative DNA helicases

Antibacterial compounds with new mechanisms of action are needed for effective therapy against drug-resistant pathogens in the clinic and in biodefense. Screens for inhibitors of the essential replicative helicases of Bacillus anthracis and Staphylococcus aureus yielded 18 confirmed hits (IC₅₀ ? 25 μM). Several (5 of 18) of the inhibitors were also shown to inhibit DNA replication in permeabilized polA-deficient B. anthracis cells. One of the most potent inhibitors also displayed antibacterial activity (MIC ～5 μg/ml against a range of Gram-positive species including bacilli and staphylococci) together with good selectivity for bacterial versus mammalian cells (CC₅₀/MIC > 16) suitable for further optimization. This compound shares the bicyclic ring of the clinically proven aminocoumarin scaffold, but is not a gyrase inhibitor. It exhibits a mixed mode of helicase inhibition including a component of competitive inhibition with the DNA substrate (K_i = 8 μM) and is rapidly bactericidal at 4 × MIC.     

Anuran species richness,complementarity and conservation conflicts in Brazilian Cerrado

Broad-scale correlations between species richness and human population suggest that processes driving species richness, mainly related to high ecological productivity, may also drive human populations. However, it is still under debate if this coincidence implies conflicts between biodiversity conservation and human development. In this paper, we analyzed the relationships among human population size, species richness and irreplaceability in Brazilian Cerrado. We analyzed a dataset with 131 species of anurans distributed in 181 cells with 1° of spatial resolution covering the biome. We found a positive correlation between human population size and anuran species richness (r = 0.46; P = 0.033 with 19.5 geographically effective degrees of freedom, v*), but the irreplaceability of each cell was poorly correlated with human population size (r = 0.075; P = 0.323; v* = 173.9). The 17 cells in the 97 optimal reserve networks contained a total human population ranging from 2942,195 to 4319,845 people, representing on average 11.8% of the human population in the entire Cerrado grid. The comparison of these observed values with 10,000 values from randomly generated networks suggests a relatively high flexibility in optimal complementarity sets for reserve selection. Our results indicated that correlation between richness and human population does not necessarily result in conflicts, given the opportunities for conciliating conservation and development. However, the analyses performed here are initial explorations within the framework of conservation biogeography, so more detailed studies are necessary to establish conservation planning at regional and local scales.     

Interleukin-1 beta and interleukin-6 gene polymorphism associations with angiographically assessed coronary artery disease in Brazilians

The inflammatory process has been considered an important mediator for the development of atherosclerosis. Interleukin-1 beta (IL1B) is a precursor of interleukin-6 (IL6) in the acute phase of inflammatory response and their levels are elevated in patients with coronary artery disease. The aim of the present study was to further investigate the association of IL-1B and IL-6 gene polymorphisms and angiographically assessed coronary artery disease (CAD) in African- and Caucasian-Brazilians. This report analyzed the IL-1B-511C>T and IL-6-174G>C polymorphisms in 667 patients (253 African-Brazilians and 414 Caucasian-Brazilians) who underwent coronary angiography. Patients with a coronary obstructive lesion ⩾50% presented a higher frequency of the IL-1B-511CC genotype (30.4%) compared to lesion-free individuals (16.5%, p = 0.032) in African- but not in Caucasian-Brazilians. No significant genotype frequency difference was identified for the IL-6-174G>C polymorphism in either ethnic groups. However, after correction for other CAD risk factors using multivariate logistic regression, both the IL-1B-511CC [Odds ratio (OR) = 2.3; p = 0.019] and the IL-6-174GG (OR = 2.0; p = 0.028) genotypes were considered independent CAD risk predictors in African-Brazilians. This report shows that the IL-1B-511C>T and IL-6-174G>C polymorphisms were associated with CAD risk in African-Brazilians and no association was detected among Caucasian-Brazilians.     

Synthesis and biological evaluation of substituted 2-phenyl-2H-indazole-7-carboxamides as potent poly(ADP-ribose) polymerase (PARP) inhibitors

A potent series of substituted 2-phenyl-2H-indazole-7-carboxamides were synthesized and evaluated as inhibitors of poly (ADP-ribose) polymerase (PARP). This extensive SAR exploration culminated with the identification of substituted 5-fluoro-2-phenyl-2H-indazole-7-carboxamide analog 48 which displayed excellent PARP enzyme inhibition with IC₅₀ = 4 nM, inhibited proliferation of cancer cell lines deficient in BRCA-1 with CC₅₀ = 42 nM and showed encouraging pharmacokinetic properties in rats compared to the lead 6.     

1,5-Benzodiazepine inhibitors of HCV NS5B polymerase

Optimization through parallel synthesis of a novel series of hepatitis C virus (HCV) NS5B polymerase inhibitors led to the identification of (R)-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-10-(6-methylpyridine-2-carbonyl)-2,3,4,5,10,11-hexahydro-dibenzo[b,e][1,4]diazepin-1-one 11zc and (R)-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-10-(2,5-dimethyloxazol-4-carbonyl)-2,3,4,5,10,11-hexahydro-dibenzo[b,e][1,4]diazepin-1-one 11zk as potent (replicon EC₅₀ = 400 nM and 270 nM, respectively) and selective (CC₅₀ > 20 μM) inhibitors of HCV replication. These data warrant further lead-optimization efforts.     

Oleanolic acid (OA) as an antileishmanial agent: Biological evaluation and in silico mechanistic insights

Although a worldwide health problem, leishmaniasis is considered a highly neglected disease, lacking efficient and low toxic treatment. The efforts for new drug development are based on alternatives such as new uses for well-known drugs, in silico and synthetic studies and naturally derived compounds. Oleanolic acid (OA) is a pentacyclic triterpenoid widely distributed throughout the Plantae kingdom that displays several pharmacological activities. OA showed potent leishmancidal effects in different Leishmania species, both against promastigotes (IC_{50 L. braziliensis} 30.47 ± 6.35 μM; IC_{50 L. amazonensis} 40.46 ± 14.21 μM; IC_{50 L. infantum} 65.93 ± 15.12 μM) and amastigotes (IC_{50 L. braziliensis} 68.75 ± 16.55 μM; IC_{50 L. amazonensis} 38.45 ± 12.05 μM; IC_{50 L. infantum} 64.08 ± 23.52 μM), with low cytotoxicity against mouse peritoneal macrophages (CC₅₀ 235.80 ± 36.95 μM). Moreover, in silico studies performed to evaluate OA molecular properties and to elucidate the possible mechanism of action over the Leishmania enzyme sterol 14α-demethylase (CYP51) suggested that OA interacts efficiently with CYP51 and could inhibit the ergosterol synthesis pathway. Collectively, these data indicate that OA is a good candidate as leading compound for the development of a new leishmaniasis treatment.     

Support vector machines to model presence/absence of Alburnus alburnus alborella (Teleostea,Cyprinidae) in North-Western Italy: Comparison with other machine learning techniques

Alburnus alburnus alborella is a fish species native to northern Italy. It has suffered a very sharp decrease in population over the last 20 years due to human impact. Therefore, it was selected for reintroduction projects. In this research project, support vector machines (SVM) were tested as possible tools for building reliable models of presence/absence of the species. A system of 198 sites located along the rivers of Piedmont in North-Western Italy was investigated. At each site, 19 physical-chemical and environmental variables were measured. We verified that performances did not improve after feature selection but, instead, they slightly decreased (from Correctly Classified Instances [CCI] = 84.34 and Cohen's k [k] = 0.69 to CCI = 82.81 and k = 0.66). However, feature selection is crucial in identifying the relevant features for the presence/absence of the species. We then compared SVMs performances with decision trees (DTs) and artificial neural networks (ANNs) built using the same dataset. SVMs outperformed DTs (CCI = 81.39 and k = 0.63) but not ANNs (CCI = 83.03 and k = 0.66), showing that SVMs and ANNs are the best performing models, proving that their application in freshwater management is more promising than traditional and other machine-learning techniques.     

Synthesis and biological evaluation of new bis-indolone-N-oxides

A series of bis-indolone-N-oxides, 1a–f, was prepared from bis(ethynyl)benzenes and o-halonitroaryls and studied for their in vitro antiplasmodial activities against Plasmodium falciparum and representative strains of bacteria and candida as well as for their cytotoxicity against a human tumor cell line (MCF7). They did not cause any haemolysis (300 μg mL⁻¹). Of the synthesized bis-indolones, compound 1a had the most potent antiplasmodial activity (IC₅₀ = 0.763 μmol L⁻¹ on the FcB1 strain) with a selectivity index (CC₅₀ MCF7/IC₅₀ FcB1) of 35.6. No potency against the tested microbial strains was observed.     

Potent and selective HIV-1 ribonuclease H inhibitors based on a 1-hydroxy-1,8-naphthyridin-2(1H)-one scaffold

Optimization studies using an HIV RNase H active site inhibitor containing a 1-hydroxy-1,8-naphthyridin-2(1H)-one core identified 4-position substituents that provided several potent and selective inhibitors. The best compound was potent and selective in biochemical assays (IC₅₀ = 0.045 μM, HIV RT RNase H; 13 μM, HIV RT-polymerase; 24 μM, HIV integrase) and showed antiviral efficacy in a single-cycle viral replication assay in P4-2 cells (IC₅₀ = 0.19 μM) with a modest window with respect to cytotoxicity (CC₅₀ = 3.3 μM).     

DNA (cytosine-5)-methyltransferase 3B (DNMT 3B) polymorphism and risk of Down syndrome offspring

Down syndrome (DS) is the most common form of human genetic mental retardation. Several polymorphisms in genes coding folic acid cycle enzymes have been associated to the risk of bearing a DS child; however, the results are controversial. S-adenosyl-l-methionine (SAM) is an important intermediate of folic acid pathway and acts as methyl donor and substrate for DNA (cytosine-5)-methyltransferase 3B (DNMT3B – EC 2.1.1.37) de novo methylation processes during embryogenesis. Recent studies suggest that a functional polymorphism of DNMT 3B in maternal genotype may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 111 mothers of DS infants (MDS) and 212 control mothers (CM) through PCR-RFLP. The observed genotypic frequencies were CC = 0.22; CT = 0.49 and TT = 0.29 in CM, and CC = 0.30; CT = 0.52 and TT = 0.18 in MDS. Allelic frequencies were C = 0.47 and T = 0.53 in CM and C = 0.56 and T = 0.44 in MDS. No deviation of HWE was observed, and both DNMT 3B rs2424913 genotype (χ2 = 4.53; DF = 1; P = 0.03) and allelic (χ2 = 4.90; DF = 1; P = 0.03) frequencies show significant differences between MDS and CM. The presence of the mutant DNMT 3B T allele decreases 30% the risk of bearing a DS child (OR = 0.69; 95% CI: 0.50–0.96; P = 0.03), and the risk is diminished up to 45% in association with the homozygous genotype (OR = 0.54; 95% CI: 0.31–0.96; P = 0.04). Our results suggest that women harboring the single nucleotide polymorphism DNMT 3B rs2424913 have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.     

Design,synthesis and biological evaluation of 3-benzyloxy-linked pyrimidinylphenylamine derivatives as potent HIV-1 NNRTIs

A novel series of 3-benzyloxy-linked pyrimidinylphenylamine derivatives (8a–8s) was designed, synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cell cultures. Most of the compounds inhibited wild-type (wt) HIV-1 replication in the lower micromolar concentration range (EC₅₀ = 0.05–35 μM) with high selectivity index (SI) values (ranged from 10 to >4870). In particular, 8h and 8g displayed excellent antiretroviral activity against wt HIV-1 with low cytotoxicity (EC₅₀ = 0.07 μM, CC₅₀ >347 μM, SI >4870; EC₅₀ = 0.05 μM, CC₅₀ = 42 μM, SI = 777, respectively), comparable to that of the marked drug nevirapine (EC₅₀ = 0.113 μM, CC₅₀ >15 μM, SI >133). In order to confirm the binding target, 8h was selected to perform the anti-HIV-1 RT assay. Additionally, preliminary structure activity relationship (SAR) analysis and molecular docking studies of newly synthesized compounds were also discussed, as well as the predicted physicochemical properties.     

Synthesis and biological evaluation of novel 2-(substituted phenylaminocarbonylmethylthio)-6-(2,6-dichlorobenzyl)-pyrimidin-4(3H)-ones as potent HIV-1 NNRTIs

A series of novel 2-(phenylaminocarbonylmethylthio)-6-(2,6-dichlorobenzyl)-pyrimidin-4(3H)-ones have been designed and synthesized. All of the new compounds were evaluated for their anti-HIV activities in MT-4 cells. Most of these new compounds showed moderate to potent activities against wild-type HIV-1 with an EC₅₀ ranging from 4.48 μM to 0.18 μM. Among them, 2-[(4-bromophenylamino)carbonylmethylthio]-6-(2,6-dichlorobenzyl)-5-methylpyrimidin-4(3H)-one 4b3 was identified as the most promising compound (EC₅₀ = 0.18 ± 0.06 μM, CC₅₀ >243.56 μM, SI >1326). The structure–activity relationship (SAR) of these new congeners is discussed.     

How to efficiently obtain accurate estimates of flower visitation rates by pollinators

Regional declines in insect pollinators have raised concerns about crop pollination. Many pollinator studies use visitation rate (pollinators/time) as a proxy for the quality of crop pollination. Visitation rate estimates are based on observation durations that vary significantly between studies. How observation duration relates to the accuracy of the visitation rate estimate is, however, unknown. We studied this relationship using six day-long observations (06:00 h–19:00 h) in leek-seed production fields (totalling 78 h). We analysed beyond which point in time observing longer did not significantly improve the accuracy of the visitation rate estimate (minimum observation duration). We furthermore explored the relationship between the minimum observation duration and visitation rate, time of day and temperature. We found that the minimum observation duration (mean ± SD: 24 ± 11.9 min) was significantly related to visitation rate, where the observation time required to obtain accurate estimates decreased with increasing visitation rate. Minimum observation duration varied greatly between days and between fields but not within days. Within days, the visitation rates differed significantly only between the hour-intervals 06:00 h–07:00 h (lowest visitation rate) and 09:00 h–11:00 h (highest rate). Minimum observation duration decreased up to around 22 °C beyond which it remained fairly stable. Surprisingly, even after three day-long observations on the same plant we found new pollinator species visiting the flowers, suggesting that species-richness estimates based on plant observations alone probably underestimate true species richness. Because especially between-day variation in visitation rate on single plants can be large, reliable estimates of the pollinator visitation rate during the plant’s flowering time require observations on multiple days. Standardising the number of pollinators rather than the time to observe (standardised pollinator timing approach: time to n-pollinator visits) may provide more consistent accurate assessments of visitation rate, especially for studies that use gradients in visitation rates to examine the contribution of pollinators to crop pollination.     

Identification of pre-zygotic reproductive and morphological barriers limiting controlled crossed seed production of triploid Acacia mearnsii

A study of the reproductive biology of black wattle (Acacia mearnsii de Wild) was conducted, specifically with regard to the compatibility of the diploid × tetraploid cross to produce a triploid variety, together with identifying ways of increasing triploid seed production. Fluorescent microscopy was used to determine pollination and fertilisation rates and to identify any pre-zygotic barriers at the stigma, style and ovary. Both diploid and tetraploid families were tested as maternal parents to establish if this was imperative to producing a triploid. Morphological measurements were documented in order to determine any incompatibilities in the cross to produce a triploid. The in vivo results showed that successful fertilisation of the ovary was possible whether one used a diploid or tetraploid maternal parent. When the maternal parent was a tetraploid, however, the pollination rate (polyads adhering to the stigma) and ovary fertilisation rates were significantly (p < 0.05) greater. Morphological measurements and observations also revealed that tetraploid floral parts were significantly (p < 0.05) larger than the diploids. The morphological size differences between the diploid and tetraploid polyads and pistils did not appear to influence the fertilisation of the ovaries and thus did not pose any identifiable barrier in the cross to produce a triploid. When considering the results from the cross to produce a triploid (2n × 4n or 4n × 2n), the diploid polyads were significantly (p < 0.05) more vigorous and suitable in fertilising the tetraploid ovaries as opposed to the reverse. Possible pre-zygotic barriers at the stigma, style or ovary were investigated and the only area that could be identified limiting seed production was within the ovary.     

Analysis of the germination rate,mitotic index and karyotype of Chromolaena barranquillensis (Hieron.) R.M. King & H. Rob.—Asteraceae

Chromolaena barranquillensis (Asteraceae) is an endemic plant of northern Colombia that has garnered economic and medicinal interest, because species from the genus Chromolaena have shown diverse biological activities. This study describes, for the first time, the karyotype, germination and mitotic indices of C. barranquillensis (Hieron.) R.M. King & H. Rob. The germination index was between 34% and 56% with an average germination rate of 1.2 ± 0.4 seeds/day. The mitotic index analysis allowed to determine the cell cycle time (4 h, 10 min) and the mitotic hours (3:00–8:00 h and 17:00 h). The mitosis time was 49 min, equivalent to ~ 20% of the cell cycle. Karyotype analysis showed that C. barranquillensis is a hexaploid species with a chromosomal formula 2n = 6x = 60 = 48 m + 12 sm, and the average chromosomal lengths were 1.7 ± 0.1 μm to 0.9 ± 0.3 μm. The Stebbins asymmetry index was 2B, and the total form percentage was ~ 41%. These results uncover differences between C. barranquillensis and Chromolaena odorata, one of the most abundant species found in the world and the most closely related species to C. barranquillensis.     

Typha × glauca dominance and extended hydroperiod constrain restoration of wetland diversity

Urban wetlands typically have few plant species. In wetlands designed to improve water quality, nutrient-rich water and highly variable water levels often favor aggressive, flood-tolerant plants, such as Typha × glauca (hybrid cattail). At Des Plaines River Wetlands Demonstration Site (Lake Co., IL), we assessed T. × glauca dominance and plant community composition under varying hydroperiods in a complex of eight constructed wetlands. Plots flooded for more than 5 weeks during the growing season tended to be dominated by T. × glauca, while plots flooded fewer days did not. Plots with high cover of T. × glauca had low species richness (negative correlation, R² = 0.72, p < 0.001). However, overall species richness of the wetland complex was high (94 species), indicating that wetlands in urbanizing landscapes can support many plant species where T. × glauca is not dominant. T. × glauca-dominated areas resisted the establishment of a native plant community. Removing T. × glauca and introducing native species increased diversity initially, but did not prevent re-invasion. Although 12 of the 24 species we seeded became established in our cleared plots, T. × glauca rapidly re-invaded. In year 1, T. × glauca regained an average of 11 ramets m⁻², and its density doubled in year 2. The likelihood of planted species surviving decreased as duration of inundation increased, and in both seeded and planted plots, graminoids had greater survivorship through year 2 than forbs across a range of water levels. Within 4 years, however, T. × glauca was the most common plant, present in 92% of the cleared plots. Simply removing T. × glauca and adding propagules to an urban wetland is not sufficient to increase diversity.     

Promoter polymorphism (−590, T/C) of interleukin 4 (IL4) gene is associated with rheumatoid arthritis: An updated meta-analysis

Rheumatoid arthritis (RA) is a chronic disease. It causes chronic inflammation of the joint. Recent studies suggested that interleukin 4 (IL4) contributes to susceptibility and severity of rheumatoid arthritis (RA). Especially, it was reported that promoter polymorphism (−590, T/C) of IL4 gene has been associated with susceptibility of RA. The aim of present study was to investigate whether the promoter polymorphism (−590, T/C) of IL4 gene is associated with the susceptibility of RA using meta-analysis. And in order to perform meta-analysis, comprehensive meta analysis program was used. Genetic models (co-dominant, dominant, recessive, and allele) were used to determine odds ratios (ORs), 95% confidence intervals (CIs), and P values. Nine case-control studies with case and control design were included in this meta-analysis. Overall, meta-analysis revealed a strong association with susceptibility of RA [OR = 1.303, 95% CI = 1.093–1.554, P = 0.003 in allele model (C vs. T); OR = 1.247, 95% CI = 1.054–1.474, P = 0.010 in dominant model (CC vs. CT + TT); OR = 2.148, 95% CI = 1.263–3.651, P = 0.005 in recessive model (CC + CT vs. TT)]. Our data demonstrated that promoter polymorphism (−590, T/C) of IL4 gene may be contributed to susceptibility of RA. However, more studies with a larger sample size are needed to provide more precise evidence.