Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study

Introduction

Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine that plays important roles in immunity and inflammation. Some studies have suggested that polymorphism in the TGFB1 gene is associated with heart disease in the general population. The purpose of the present study was to determine whether common single-nucleotide polymorphisms (SNP) in the TGFB1 gene are associated with ischaemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and to investigate the influence of smoking on any association.

Methods

PCR-based assays were used to determine the genotypes of TGFB1 SNPs including TGFB1-509 C/T (rs1800469, in the promoter region), +868 T/C (rs1800470, in exon 1) and +913 G/C (rs1800471, in exon 1) in 414 subjects with established RA. Genotyping for the +868 SNP was also carried out on a second study population of RA patients (n = 259) with early disease. Serum levels of TGF-beta1 were measured using a commercial ELISA kit. Smoking history and IHD/MI status were obtained on each patient. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses.

Results

The heterozygous genotype of TGFB+868 was associated with an increased risk of IHD (OR 2.14, 95% CI 1.30 - 3.55) and MI (OR 2.42, 95% CI 1.30-4.50), compared to the homozygous genotypes combined. Smoking was an independent risk for IHD and MI, and evidence of interaction between smoking and TGFB+868 was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the TGFB1+868 TC genotype and smoking (OR 2.75, 95% CI 1.59-4.75; and OR 2.58 95% CI 1.33-4.99, respectively), independent of other cardiovascular risk factors. The association of the +868 TC genotype and evidence of +868 TC-smoking interaction with IHD were replicated in a second population of RA patients with early disease. Serum TGF-beta1 levels were not associated with TGFB1 genetic variations, smoking or IHD/MI status.

Conclusions

Interaction between smoking and polymorphism in the TGFB1 gene may influence the risk of IHD and MI in patients with RA.     

A genome-wide screen in yeast identifies specific oxidative stress genes required for the maintenance of sub-cellular redox homeostasis

Maintenance of an optimal redox environment is critical for appropriate functioning of cellular processes and cell survival. Despite the importance of maintaining redox homeostasis, it is not clear how the optimal redox potential is sensed and set, and the processes that impact redox on a cellular/organellar level are poorly understood. The genetic bases of cellular redox homeostasis were investigated using a green fluorescent protein (GFP) based redox probe, roGFP2 and a pH sensitive GFP-based probe, pHluorin. The use of roGFP2, in conjunction with pHluorin, enabled determination of pH-adjusted sub-cellular redox potential in a non-invasive and real-time manner. A genome-wide screen using both the non-essential and essential gene collections was carried out in Saccharomyces cerevisiae using cytosolic-roGFP2 to identify factors essential for maintenance of cytosolic redox state under steady-state conditions. 102 genes of diverse function were identified that are required for maintenance of cytosolic redox state. Mutations in these genes led to shifts in the half-cell glutathione redox potential by 75-10 mV. Interestingly, some specific oxidative stress-response processes were identified as over-represented in the data set. Further investigation of the role of oxidative stress-responsive systems in sub-cellular redox homeostasis was conducted using roGFP2 constructs targeted to the mitochondrial matrix and peroxisome and E(GSH) was measured in cells in exponential and stationary phase. Analyses allowed for the identification of key redox systems on a sub-cellular level and the identification of novel genes involved in the regulation of cellular redox homeostasis.     

Molecular characterization of a 21.4 kilobase antibiotic resistance plasmid from an α-hemolytic Escherichia coli O108:H- human clinical isolate

This study characterizes the 21.4 kilobase plasmid pECTm80 isolated from Escherichia coli strain 80, an α hemolytic human clinical diarrhoeal isolate (serotype O108:H-). DNA sequence analysis of pECTm80 revealed it belonged to incompatibility group X1, and contained plasmid partition and toxin-antitoxin systems, an R6K-like triple origin (ori) replication system, genes required for replication regulation, insertion sequences IS1R, ISEc37 and a truncated transposase gene (Tn3-like ΔtnpA) of the Tn3 family, and carried a class 2 integron. The class 2 integron of pECTm80 contains an intact cassette array dfrA1-sat2, encoding resistance to trimethoprim and streptothricin, and an aadA1 gene cassette truncated by the insertion of IS1R. The complex plasmid replication system includes α, β and γ origins of replication. Pairwise BLASTn comparison of pECTm80 with plasmid pE001 reveals a conserved plasmid backbone suggestive of a common ancestral lineage. Plasmid pECTm80 is of potential clinical importance, as it carries multiple genes to ensure its stable maintenance through successive bacterial cell divisions and multiple antibiotic resistance genes.     

Preliminary observations on the response of Chironex fleckeri (Cnidaria: Cubozoa: Chirodropida) to different colors of light

Cubozoans are well known for their attraction to light and light-colored objects. Two highly venomous types are a public safety concern in Australian waters and elsewhere: Chironex fleckeri, long considered the world's deadliest animal and colloquially called the box jellyfish; and the irukandjis, a group of at least 10 species that cause various degrees of debilitating illness. We were asked by the tourism industry whether there might be a color of light that box jellyfish and irukandjis are not attracted to, such that nighttime diving activities might pose less risk of being stung. Our preliminary trials with Chironex fleckeri indicated a marked positive response to lights of white, red, yellow, green, orange, and blue. All colors elicited a strong and directed attraction to light; however, medusae slowed down their pulsation rate, streamed out their tentacles, and performed a series of figure-eight patterns back and forth through the lighted area when exposed to blue light, which we interpreted as feeding behavior. This compares curiously with a report subsequent to our testing, in which the small, mangrove-inhabiting cubomedusa Tripedalia cystophora and the beach-dwelling Chiropsella bronzie demonstrate a peak sensitivity to blue-green light in the region of 500 nm, and that the former is behaviorally attracted to blue and green light, but ignores red. This leaves open the possibility that Irukandji species, which are more closely related to Tripedalia than to Chironex, may be blind to red.     

Population structure of Helicobacter pylori among ethnic groups in Malaysia: recent acquisition of the bacterium by the Malay population

Background  

Helicobacter pylori is a major gastric bacterial pathogen. This pathogen has been shown to follow the routes of human migration by their geographical origin and currently the global H. pylori population has been divided into six ancestral populations, three from Africa, two from Asia and one from Europe. Malaysia is made up of three major ethnic populations, Malay, Chinese and Indian, providing a good population for studying recent H. pylori migration and admixture.     

Non-pertussis components of combination vaccines: problems with potency testing.

Vaccines comprising combinations of diphtheria, tetanus and pertussis (DTP) with Haemophilus influenzae type b polysaccharide-protein conjugate (Hib), inactivated poliomyelitis virus (IPV) and hepatitis B virus (HBV) are already available, and new combinations using acellular pertussis components in a triple vaccine (DTaP) are under development. Evidence to date has shown that control of the efficacy, safety and stability of combination vaccines cannot be based on information already available on the individual components or existing licensed formulations. Several examples of immunological interference between components of a combination vaccine have been observed both in clinical trials and in laboratory tests. Examples of these for D, T and Hib components in DTP and DTaP combinations have been investigated.